TW200307684A - Azepinoindole and pyridoindole derivatives as pharmaceutical agents - Google Patents

Abstract

Compounds, compositions and methods for modulating the activity of receptors are provided. In particular compounds and compositions are provided for modulating the activity of receptors and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder directly or indirectly related to the activity of the receptors.

Description

200307684 (ii) Description of the invention: The related application is based on 35 USC 119 (e), claiming priority benefit of US Provisional Application No. 60 / 383,574, filed on May 24, 2002 to Richard Martin et al. Titled π-nuclear acceptor nitro-indole and pyridoindole modulators ". The disclosures of the applications cited above are hereby incorporated by reference in their entirety. [Technical Field to which the Invention belongs] The present invention provides compounds, compositions, and methods for modulating receptor activity, and for treating, preventing, or ameliorating one or more symptoms of a disease or disorder associated with the receptor activity. [Prior art] Nuclear receptors Nuclear receptors are a supergroup of regulatory proteins that are structurally and functionally related and are receptors such as steroids, retinoids, vitamin D, and thyroid hormones (see, for example, Evans (1988) 2 Early: 889-895). These proteins are cis-acting elements that bind to the promoter of their target genes and modulate gene expression in response to the ligand of the receptor. Nuclear receptors can be classified based on their DNA-binding properties (see, for example, Evans, supra, supra, and Glass (1994) £ & zifocr · / 5: 391-407). For example, a class of nuclear receptors includes corticoids, estrogen, androgens, luteinizing agents, and mineral corticosteroid receptors, which bind to homodimers to reverse hormone response elements organized by repeats (HRE) (see, for example, Glass, supra). Types of second receptors, including retinoic acid, thyroid 85585 200307684 hormones, vitamin d3, fatty acid / peroxisome proliferators (meaning peroxisome proliferator activated receptor (PPAR)) And humectin-activated, which have a common counterpart (retinoid X receptor) (meaning RXR, also known as 9-cis retinoic acid receptor; see, eg, Levin et al. (1992) Λ / α such as rd55: 359-361 'and Heyman et al. (1992) Ce // 诏: 397-406) binding to HRE 〇RXR is unique in nuclear receptors because of its DNA is bound in homodimers, and for many other nuclear receptors, heterodimer counterparts are required to bind DNA (see, eg, Mangelsdorf et al. (1995) C⑹ 53: 841-850). The receptors described below are called subtype II nuclear receptor subgroups, and include many who have been established or implicated as important regulators of gene expression. There are three RXR genes (see, for example, Mangelsdorf et al. (1992) Genes Dev · (5: 329-344) encoding RXRa,-/ 3, and -r, all of which are capable of heterodimerization with any kind of π receptor However, it has been shown to be preferential for different RXR subtypes through in vivo counterpart receptors (see, for example, Chiba et al. (1997) Mo / · Ce // · So 0 / · / 7: 3013-3020). In adult livers, RXRa is the most abundant of these three RXRs (see, for example, Mangelsdorf et al. (1992) Gew⑵ (5 ·· 329-344)), which indicates that it is involved in liver function regulated by type II nuclear receptors. It may have a prominent role. See also Wan et al. (2000) Afo / · Ce // · 5 Magic / 20: 4436-4444. Orphan nuclear receptors are included in the nuclear receptor superfamily of regulatory proteins. Those whose ligands are known nuclear receptors, and those lacking known ligands. The nuclear receptors that fall into the species described below are called orphan nuclear receptors. Searching for an orphan receptor activator has led to A previously unknown message channel was found (see, for example, Levin et al. 85585 200307684, (1992), with Former source, with Heyman et al. (1992), same source as above. For example, bile acids have been reported to be involved in physiological processes, such as cholesterol catabolism, which is paired with the farnesin X receptor (below). Since the products of intermediate metabolism are known to act as transcriptional regulators in bacteria and yeast, such molecules can serve similar functions in higher organisms (see, for example, Tomkins (1975) Yoshi ce / 59: 760_763 and O 'Malley (1989) five mfocrz · fegy / 25: 1119-1120). For example, one of the biosynthetic pathways in higher eukaryotes is the mevalonate pathway, which causes cholesterol, bile acids, porphyrins Synthesis of morpholine, polyterpene alcohol, ubiquinone, carotenoids, retinoids, vitamin D, steroid hormones, and farnesylated proteins. Farnesin-like receptors Farnesin-like receptors (originally isolated as RIP14 (Retinoid X Receptor Interaction Protein-14), see, for example, Seol et al. (1995) M (9 /. P: 72-85), is a member of the nuclear hormone receptor superfamily, and is mainly related to Liver, kidney, and intestine (see, for example, Seol, etc.) Humans, as mentioned above, and Formen et al. (1995) Ce // ^: 687-693). It acts as a heterodimer with the retinoid X receptor (RXR) and binds to the activation of the target gene Response elements in the seed to regulate gene transcription. The farnesin X receptor-RXR heterodimer system binds to the inverted repeat-1 (IR-1) response element with the highest affinity, in which the hexamer bound to the receptor is separated by a single nucleotide. The farnesin X receptor system is part of an interconnected process, because the receptor system is activated by bile acids (the final product of cholesterol metabolism) (see, for example, Makishima et al. (1999) Sd 1362_1365, Parks et al. ( 1999) Sd⑼1365-1368, Wang et al. (1999) Mo / · Ce // · 3 ··· 543-553), which are used to inhibit gall 85585 200307684 steroid catabolism. See also Urizar et al. (2000) / 5ζ · ο / · C% Fox 275: 39313-39317. Nuclear receptor and disease nuclear receptor activity, including farnesin-like X receptors, and / or orphan nuclear receptor activity are 'associated with a variety of diseases and conditions, including but not limited to hyperlipidemia and high cholesterol' And its complications, including but not limited to coronary artery disease, heart pain, carotid artery disease, stroke, cerebral arteriosclerosis and xanthomas (see, for example, International Patent Application Publication WO 00/57915), osteoporosis and vitamin deficiency (See, e.g., U.S. Patent 6,316,5103), hyperlipoproteinemia (see, e.g., International Patent Application Publication WO 01/60818), excessive blood triglycerides, fat metabolism disorders, peripheral occlusive disease, hemorrhagic stroke, hyperglycemia And diabetes (see, for example, International Patent Application Publication WO001 / 82917) 'Illnesses associated with insulin resistance, including clusters of symptoms, symptoms, or conditions that constitute " symptom cluster X ", such as glucose Tolerance, increase in plasma triglycerides and decrease in high-density lipoprotein cholesterol concentration, hypertension, hyperuricemia, small, dense, low-density Protein particles with higher circulating plasminogen activator inhibitors4, atherosclerosis and gallstones (see 'e.g., International Patent Application Publication WO 00 / 37〇77), skin and mucosa Illnesses (see, for example, U.S. Patent Nos. 6,184,215 and 6,187,814 and International Patent Application Gazette 98/32444), obesity, acne (see, for example, International Patent Application Gazette WO 00/4 9992) and cancer, bile depression Stagnation, Parkinson's disease, and Alzheimer's disease (see, for example, International Patent Application Publication WO 00/17334). Nuclear receptors, including farnesin-like receptors and / or orphan nuclear receptors, whose activity 85585 200307684 is related to physiological processes, including but not limited to triglyceride metabolism, catabolism, transport or absorption, bile acids Metabolism, catabolism, transport, absorption, reabsorption or bile pooling composition, cholesterol metabolism, catabolism, transport, absorption or reabsorption. Cholesterol 7α-hydroxylase gene (CYP7A1) transcription (see, for example, Chiang et al. (2⑻〇) ·· · CW milk: 1091㈣924), HDL metabolism (see, for example, Urizar et al. (2000) 1 / • Ga α. No. 275: 39313_39317), hyperlipidemia, bile stagnation and increased cholesterol outflow and increased Ατρ combined with cassette transporter protein (ABC1) performance (see, for example, International Patent Application Publication WOOO / 78972) The modulation is also modulated by or influenced by farnesin and receptor. Therefore, there remains a need for compounds, compositions, and methods for modulating the activity of nuclear receptors, including farnesin-like orphan nuclear receptors. This combination is used to treat, prevent or ameliorate one or more symptoms of a disease or condition in which nuclear receptor activity is implicated. [Summary of the Invention] The present invention provides a pharmaceutical composition and method for modulating nuclear receptor activity. In particular, compounds are provided for use in compositions and methods to modulate farnesin-like X-dimer and / or orphan nuclear receptors. In some specific cases, the compound is nitrogen sulfonate or Edo benzoate, a derivative. In the specific embodiment, the compound provided herein is a farnesin-like x stylistic "activator". In another embodiment, the compounds provided herein are antagonists of the farnesin x receptor. In another specific embodiment: the compound provided in this example is a reverse activator, a quasi-kinetic agent or a partial antagonist of a farnesin-like receptor. In certain embodiments, the activator exhibiting 85585 200307684 low efficacy is an antagonist. In a specific embodiment, the compounds provided herein for use in the compositions and methods have formula (I) or formula (II):

Or a pharmaceutically acceptable derivative thereof, wherein: η is 0 to 4; A is -N (R9)-, -0-, or · 8 (〇χ- (where t is 0 or 2); R1 is as appropriate Substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally Substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, -〇Rl 4, -N (R15) R16, -N (R17) N (R15) R16,- C (0) R18, -C (〇) 〇14, (⑸0R14, -C (0) SR14, ^ (Ο) Ν (Κ15) R16, _C (0) N = 服 i% -C (〇) N ( Ri 7) n (ri 5) ri 6; R2 is hydrogen or optionally substituted alkyl; or R1 and R2 together with the atoms to which they are attached form a cycloalkyl optionally substituted, optionally substituted Heterocyclyl, optionally substituted aryl or optionally substituted heteroaryl ring; 85585 -11- 200307684

R3 is optionally substituted alkyl, optionally substituted feminine, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aralkyl , Optionally substituted heteroaryl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -C (0) Rl G, -CXCOOR10, -S (0) 2 R1 〇, -CXCOISKR11) 1110, -CXOMR11 MR12) 1110, -NCR11) C (0) R! 0--N (R! 1) C (0) N (R12) R10 '-NCR11) C (0) N (R12) N (R13) R! °, -N (R ") C (0) OR10, -P (0) 0R1 () or -P (〇) (〇R19) 〇R10; R4 is hydrogen, which may be substituted as appropriate Alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted Heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, -C (0) Ri8, -C (0) 0R2 0, -C (0) N (R21) R2 2 or -C (0) N (R4 2) Nβ ^ R5, R6 and R7 are each independently hydrogen, optionally substituted alkyl, optionally substituted aralkyl, optionally substituted Heteroaralkyl, -OrH; -S (0) 2R14, -N (R15) R16, _C (〇) R18, _C (〇) 〇r20 or -C (〇) n (r21) r22; or R4 and R7 , Or R4 and R6, or R5 and R7, or R5 and R6 together to form optionally substituted cycloalkyl, optionally substituted heterocyclyl, or optionally substituted cyclofluorenyl ring; and other R4, R5 , R6 and R7 are as described above; or R4 and R5 together form a keto group; and R6 and R7 are both described above; or ^ and & 7 together form a keto group; and R4 and R5 are as described above; each R8 is independently selected From including hydrogen, optionally substituted alkyl, optionally substituted amidino, optionally substituted alkynyl 'optionally substituted aryl, optionally substituted heteroaryl, self-based, Cyano, cyano, nitro, _C (0) 0R2 3, hepta (〇) n (r24) r25, _c (〇) r26, 〇r27 and _n (r28) r29; 85585 -12- 200307684 , Optionally substituted alkyl or -S (〇) 2R43; ^ (^^ ", ^^, ^^, and ^^ are selected from ⑷ or 如 as follows: Ruler 11, Ri2, R13, and R19 are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally Optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted arylhexyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaryl Alkyl; and R1G is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted Substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; or (b) R1G and R11, and / or R1G and R12, and / Or R10 and R13, and / or R1G and R19, and / or RH and R12, and / or R12 and R13, together with the atoms to which they are attached, form optionally substituted heterocycles or optionally substituted heterocycles Aryl ring; while other rigs, R11, R12, R13 and R19 are selected from ⑻ as above; R14, R15, R16 and R17 are selected from ⑻ or ⑼: ⑻R14, R15, R16 and R17 are each independently Hydrogen, optionally substituted alkyl, optionally substituted amidino, optionally substituted alkynyl, optionally substituted Alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; or ( b) R15 and R16 together with the nitrogen atom to which they are connected form a heterocyclic ring optionally substituted or a heteroaryl ring optionally substituted, and Ri4 and R17 are selected as above;

R18 is optionally substituted alkyl, optionally substituted alkenyl, optionally 85585 -13- 200307684 optionally substituted decyl, optionally substituted ring pit, optionally substituted aryl, Optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaryl group; r2G, R21, R22, and R42 are as follows: Or (b): ⑻R20, R21, R22 and R42 are each independently hydrogen, optionally substituted alkyl, optionally substituted fluorenyl, optionally substituted alkynyl, optionally substituted ring Base, optionally substituted aryl, optionally substituted aryl bond * group, optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; or ( b) R21 and R22 and the nitrogen atom to which they are connected form a heterocyclic ring optionally substituted heteroaryl ring or a heteroaryl ring optionally substituted; and R20 and R42 are selected as above; R23 , R24, R25, and R26 are selected from the following ⑻ or ·: ⑻ R23, R24, R25, and R26 are each independently hydrogen Optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aralkyl, Optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; or (b) R24 and R25 and the nitrogen atom to which they are attached together to form a optionally substituted Heterocyclic group or optionally substituted heteroaryl ring, and R23 and R26 are selected from ⑻ as above; R27, R28 and R29 are selected from ⑻ or (b) as follows: ⑻R27, R28 and R29 are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally Substituted heteroaryl, optionally substituted heteroaralkyl, -C (0) R3 G, -C (0) 0R31 or -C (0) N (R3 2) R3 3; or (b) R2 8 85585 -14- 200307684, together with R29 and the nitrogen atom to which they are connected, form a heterocyclic ring optionally substituted or a heteroaryl ring optionally substituted, and R27 is Select as above: R30 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted block, optionally substituted cycloalkyl, optionally substituted aromatic Base, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; R31 is optionally substituted alkyl, optionally Optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, Optionally substituted heteroaryl or optionally substituted heteroaralkyl; R32 and R33 are selected from ⑻ or (b) below. ⑻ R32 and R33 are each independently hydrogen and optionally substituted alkane Base, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aryl group, optionally substituted by Shen Heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaryl ; Or (b) R32 and R33 and the nitrogen atom to which they are connected together to form a heterocyclic ring optionally substituted or a heteroaryl ring optionally substituted; R43 is optionally substituted alkyl, optionally Substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally Case substituted heteroaryl or optionally substituted heteroaralkyl; each R1-R33, R42 and R43, when substituted, is substituted with one or more substituents each independently selected from Q1; 85585- 15- 200307684 Q1 is auto-, pseudo-, hydroxy-, keto-, thio-, nitrile-, nitro-, formamyl-, mirror-based, light-carbonyl, carbonyl-based, alkyl-based, 1-alkyl-based, polyhalogenated : Base, aminoalkyl, diaminoalkyl, alkenyl containing 1 to 2 double bonds, alkynyl containing 1 to 2 double bonds, cycloalkyl, cycloalkylalkyl, heterocyclyl, Heterocyclylalkyl, aryl, heteroaryl, aralkyl, arylfluorenyl, aralkynyl, heteroaralkyl, trialkylsilyl, dialkylarylsilyl, alkane Diarylsilyl, triarylsilyl, alkylene, arylalkylene, alkylcarbonyl, cycloalkylcarbonyl, heterocyclylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, alkoxycarbonyl Alkyl, aryloxycarbonyl, aryloxycarbonylalkyl, aralkyloxycarbonyl, aralkyloxycarbonylalkyl, arylcarbonylalkyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, Arylaminocarbonyl, diarylaminocarbonyl, aralkylaminocarbonyl, alkoxyaryloxy, heteroaryloxy, heteroarylalkoxy, heterocyclyloxy, cycloalkoxy, all Fluoroalkoxy, alkenyloxy, alkynyloxy, aralkoxy, alkcarbonyloxy, arylcarbonyloxy, aralkylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, aryl Alkoxycarbonyloxy, aminocarbonyloxy, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylarylaminocarbonyloxy, diarylaminocarbonyloxy, guanidine, isopropyl Thiourea, formamyl, alkylformamyl, arylformamyl, aminothiocarbonyl, alkylaminothiocarbonyl, arylaminothiocarbonyl, amine, aminoalkyl , Alkylaminoalkyl, dialkylaminoalkyl, arylaminoalkyl, diarylaminoalkyl, alkylarylaminoalkyl, alkylamino, dialkylamino, alkylamino Aryl, arylamino, diarylamino, arylarylamino, carbonylamino, alkoxycarbonylamino, aralkyloxycarbonylamino, arylcarbonylamino, arylcarbonylaminoalkyl , Aryloxycarbonylaminoalkyl, aryloxyarylcarbonyl 85585 -16- 200307684 amine, aryloxycarbonylamino, alkylsulfonylamino, arylcontinylamino, heteroaryl Phenylamino, heterocyclic phenylamino, heteroarylthio, azide, diazenyl, -N + (R34) (R35) R36, _p ^^ R37h, -C ^ OXR37 ) 2, -N (R38) C (0) R39, dialkylphosphonic acid group, alkylarylphosphonic acid group, diarylphosphonic acid group, hydroxyphosphonic acid group, alkylthio group, arylthio group, King gas-based thio group, super carbonyl group, thio group, thiocyano group, isothiocyano group, sulfenylsulfenyloxy group, alkylsulfonyloxy group, arylsulfinyloxy group, arylsulfonyl group Alkyloxy, hydroxysulfonyloxy, alkoxysulfonyloxy, aminesulfonyloxy, alkylamino Sulfonyloxy, dialkylaminosulfonyloxy, arylaminosulfonyloxy, diarylaminosulfonyloxy, alkylarylaminosulfonyloxy, halostone, alkyl Sulfinylsulfenyl, alkylsulfinyl, arylsulfinyl, arylsulfinyl, hydroxysulfinyl, alkoxysulfinyl, aminosulfinyl, alkylamino% fluorenyl, Dialkylaminosulfonyl, arylaminosulfonyl, diarylaminosulfonyl or alkylarylaminosulfonyl; or two Q1 groups, the substituted atom system of which is 2 Or 丨, 3 arranged together to form an alkylene group, an oxyalkylene group, an alkylene dioxy group, a thioalkyleneoxy group or an alkylene dithiooxy group; or two Q1 groups, which are substituted for the same atom Together form an alkylene group; R, r3 5 and r3 6 are each independently hydrogen, alkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl or heterocyclylalkyl; R37 is Hydroxy, alkoxy, aralkoxy, alkyl, heteroaryl, heterocyclyl, aryl, or -NR4GR41; R4G and R41 are each independently hydrogen, alkyl, aralkyl, aryl, heteroaryl, Heteroaralkyl or heterocyclyl, or 85585 -17- 200307684 R 4 0 and R41 together form a secondary, nitrogen, oxygen, or sulfur secondary dry group; R3 8 is hydrogen, alkyl, aryl, aryl, heteroaryl, heteroaryl, Heterocyclyl or heterocyclyl; and R3 9 is alkoxy, aryloxy, alkyl, heteroaryl, heterocyclylaryl, or -N (R40) R41; each Q1 is independently Substituted, or substituted by one or more substituents each independently selected from Q2; each Q2 is independently a southern group, a pseudofluorenyl group, a hydroxyl group, a keto group, a thio group, a nitrile, a nitro group, a formyl group, a mirror group, Via carbonyl, via alkyl, alkyl, halo, multifunctional alkyl, aminoalkyl, diaminoalkyl, alkenyl containing 1 to 2 double bonds, 1 to 2 reference bonds Alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, heteroaryl, aralkyl, arkenyl, aralkynyl, heteroaralkyl, trioxane Alkylsilyl, dialkylarylsilyl, alkyldiaryl sulfanyl, triaryl sulfonyl, oxenyl, arylsulfinyl, alkylcarbonyl, cycloalkylcarbonyl, heterocyclylcarbonyl , Arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, alkoxycarbonyl Alkyl, aryloxycarbonyl, aryloxycarbonylalkyl, aralkyloxycarbonyl, aralkyloxycarbonylalkyl, arylcarbonylalkyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl , Arylaminocarbonyl, diarylaminocarbonyl, aralkylaminocarbonyl, alkoxyaryloxy, heteroaryloxy, heteroarylalkoxy, heterocyclyloxy, cycloalkoxy, Perfluoroalkoxy, alkenyloxy, alkynyloxy'aralkoxy, alkylcarbonyloxy, arylcarbonyloxy, aralkylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, Aralkyloxycarbonyloxy, aminocarbonyloxy, alkylaminocarbonyloxy, 85585 -18- 200307684 dialkylaminocarbonyloxy, alkylarylaminocarbonyloxy, diarylaminocarbonyl Oxygen, guanidine, isothiourea, formamyl, alkylformamyl, arylformamyl, aminothiocarbonyl, alkylaminothiocarbonyl, arylaminothiocarbonyl, amino, aminoalkyl , Alkylaminoalkyl, dialkylaminoalkyl, arylaminoalkyl, diarylaminoalkyl, alkylarylaminoalkyl, alkylamino, dialkylamino, haloalkylamine base, Amine, diarylamino, alkylarylamino, alkylcarbonylamino, alkoxycarbonylamino, arylalkoxycarbonylamino, arylcarbonylamino, arylcarbonylaminoalkyl, aryl Oxycarbonylaminoalkyl, aryloxyarylcarbonylamino, aryloxycarbonylamino, alkylsulfonylamino, arylmethylamino, heteroarylpyridylamino, hetero Cycloalkylamino, heteroarylthio, azide, diazonium, -1 ^ (1134) (1135) 1136, hydrazone (1137) 2, P (0) (R37) 2, -〇P (〇) (R37) 2, -N (R38) C (0) R39, dialkylphosphonic acid group, alkylarylphosphonic acid group, diarylphosphonic acid group, hydroxyphosphonic acid group, alkane Thio, arylthio, perfluoroalkylthio, hydroxycarbonylalkylthio, thiocyano, isothiocyano, thioalkylideneoxy, thioalkyloxy, aryloxy Fluorenyloxy, arylsulfonyloxy, carboxypentaphenyloxy, carbamophenyloxy, aminesulfonyloxy, alkylaminosulfonyloxy, dialkylaminosulfonyloxy , Arylaminosulfonyloxy, diarylaminosulfonyloxy, alkylarylaminosulfonyloxy, fluorenylsulfinyl, Homosulfenyl, alkylsulfenyl, arylsulfenyl, arylsulfonyl, hydroxysulfonyl, alkoxysulfonyl, aminosulfonyl, alkylaminosulfonyl, dioxane Aminosulfonyl, arylaminosulfonyl, diarylaminosulfonyl or alkylarylaminosulfonyl; or two Q2 groups, the substituted atom system of which is 1, 2 or 1, 3 arrangement to form an alkylene, oxyalkylene, alkanedioxy, thioalkyloxy or thio85585 -19- 200307684 group dithiooxy group; or two Q2 groups' It replaces the same atom and forms a secondary group together, with the proviso that if R8 is hydrogen or -0CH3, then R3 is not hydrogen, methyl, ethyl, -ch2c6h5, -ch (ch3) c6h5, ch ( ch3) naphthyl or -c (o) oc2h5, with the proviso that if R3 is hydrogen, then R8 is not hydrogen, nitro, lower alkoxy, i- or light-based. The group R-R9 is selected so that the formed compound has nuclear receptor modulating activity, such as in at least one of the tests described herein, such as farnesin X receptor antagonist or activator activity, And in certain embodiments, the ICw or ECw is below about 100 / zM. Regarding the compounds provided herein, the IC5 () or EC5 () values of farnesin X receptors are, in certain embodiments, less than about 50, 25, 10, 1 / αM, 1 〇〇ηΜ, ι〇ηΜ or 1 nM 〇 We are also interested in any pharmaceutically acceptable derivatives, including salts, esters, dilute alcohol ethers, associate esters, solvents of the compounds described herein Compounds, hydrates and prodrugs. Pharmaceutically acceptable salts, including but not limited to amine salts, such as, but not limited to, N, N, -dimethylethylenediamine, chloroprocaine choline, ammonia, diethanolamine and other hydroxyalkylamines, Ethylenediamine, Methylglucosamine, Procaine, N-Usylphenethylamine, 2-Chloromethyl-2_tetramethylethyl-1,1-methylmethylbenzimidazine, triethylamine and others Alkyl amines, hexachloride wells and sulfanyl) aminomethyl @; test metal salts, such as but not limited to noodles, potassium, and sodium; test metal salts, such as but not limited to barium, M deficiency; transition metals Salts, such as but not limited to zinc, Ming, and other metals [such as, but not limited to, 85585 200307684 粦 广 饷 and disodium hydrogen phosphate; and also including but not limited to the sleep of mineral acids, Lu Ru, but not limited to hydrochloride and sulfuric acid Salts; and salts of organic acids: limited to acetate, cut A concealed # «4 kernels not frequent fruit salt, tartrate, citrate, blood«, salt, butyrate, valerate and reaction Succinic acid ^ Provided with a pharmaceutical composition for appropriate route and mode of administration: its effective date-or more of the compounds provided herein, or combined drugs Derivatives that transmit an effective amount to treat, predict, or treat one or more of the diseases or conditions ^% More than one dollar, m㈣ or conditions are nuclear receptors II, including farnesoid X receptors And / or orphan nuclear receptor activity or

☆ Wen Qi's influence, or its involvement in nuclear receptor activity, including farnesin X and red orphan nuclear receptor activity. Effective amounts and concentrations are effective to ameliorate any symptoms of any disease or condition. / The present invention provides a method or method for treating, preventing or ameliorating a disease or condition, wherein the child's disease or condition is through nuclear receptor activity, including farnesin X receptor and / or orphan nuclear receptor activity All, or in which, the receptor activity is implicated. Such methods include methods for treating, preventing, and ameliorating one or more symptoms. The symptoms of children are hypercholesterolemia, hyperlipoproteinemia, triglycerides, dyslipidemia, hyperglycemia, diabetes, dyslipidemia, Atherosclerosis, gallstone disease, acne vulgaris, acne-like skin symptoms, diabetes, Parkinson's disease, cancer, Alzheimer's disease, inflammation, immunological disorders, lipid disorders, obesity, to disrupt epidermal barrier function Features < Symptoms, hyperlipidemia, bile stagnation, peripheral occlusive disease, hemorrhagic stroke, epidermal or mucosal disturbances of differentiation or hyperproliferative symptoms or cardiac and vascular disorders using one or more of the compounds provided herein or Its medicine 85585 -21- 200307684 is a scientifically acceptable derivative. It also provides the use of the compound bodies provided herein, including fasquazine-like compounds, to modulate compounds and compositions provided in nuclear receptors and / or orphan nuclear receptors. . Ben again

Detection of receptor and / or orphan nuclear receptor activity In class H farnesin X assays, the assays provided by You & Engineering, including this text, are active. These methods include inhibiting the activity of fascine-like / +, brushing and palatal ganglia nuclear receptors, oestrogen X stylistics, and / or orphan nuclear receptors. It is also a method for reducing cholesterol content in a patient in need by administering a compound or composition. As mentioned in the following: a method for modulating bile metabolism with the compounds and compositions provided herein. Methods of treating one or more symptoms of a disease or condition affected by cholesterol, triglyceride or bile acid content by administering one or more of the compounds and compositions provided herein are also provided. Methods for reducing blood polycholesterol content, and directly or indirectly modulating cholesterol metabolism, catabolism, synthesis, absorption, reabsorption, secretion or excretion 'are provided by administering the requested compounds and compositions provided herein Triglyceride content, and methods for directly or indirectly modulating triglyceride metabolism, catabolism, synthesis, absorption, reabsorption, secretion, or excretion, are provided by administering the requested compounds and compositions provided herein. Methods for reducing bile acid content, and directly or indirectly modulating bile acid metabolism, catabolism, synthesis, absorption, reabsorption, secretion, excretion or bile sinks 85585 -22 · 200307684 Set composition by administering provided herein The requested compounds and compositions are provided. A method of treating, preventing, or ameliorating one or more symptoms of a disease or condition that affects cholesterol, triglyceride, or bile acid content, or any combination thereof, is provided using the compounds and compositions provided herein. To provide a method for treating, preventing or improving one or more symptoms of hyperlipidemia, hypercholesterolemia, hyperglyceride, lipid disorders and lipometabolism, and treatment of complications thereof. Methods of treating, preventing or ameliorating one or more symptoms of atherosclerosis, atherosclerotic disease, atherosclerotic disease event, and atherosclerotic heart and vascular disease are also provided. In addition, the present invention also provides a method for preventing or reducing the risk of an atherosclerotic disease event at the first or subsequent occurrence, which comprises administering to a patient at risk of such an event a prophylactically effective amount of a compound or composition of the present invention. The patient may already have an atherosclerotic disease at the time of administration or may be at risk of developing the disease. In another aspect, the method of the present invention is also used to remove cholesterol from tissue deposits, such as atherosclerotic plaques or xanthomas in patients with atherosclerotic diseases, which are clearly indicated by clinical signs, For example, colic, trek, noisy, those who have suffered a myocardial infarction or transient hemorrhagic hair, or those diagnosed by vascular X-ray, sonic recording or MRI. Methods of using the compounds and compositions provided herein to treat, prevent or ameliorate one or more symptoms of diabetes, and to treat complications of diabetes are also provided. 85585 • 23 · 200307684 also provides the use of compounds and compositions provided herein to treat, prevent, or improve insulin insensitivity or resistance—or multiple reductions—and to treat complication of insensitivity or resistance to tenanthin. method. Methods of using the compounds and compositions provided herein to treat, prevent or ameliorate one or more symptoms of hyperglycemia, and to treat complications of hyperglycemia are also provided. Provides methods for treating, preventing, or ameliorating any condition associated with diabetes, hyperglycemia, or insulin resistance, including the formation of clusters of disease states, symptoms, or conditions. In addition, the present invention also provides A method for preventing or reducing the risk of developing hyperglycemia, insulin resistance, or diabetes in a patient, comprising administering a prophylactically effective amount of a compound or composition of the present invention to a patient at risk of such an event. By administering a compound or composition provided herein, a method for treating, preventing or ameliorating one or more symptoms of bile stagnation, and for treating complications of bile stagnation. Therefore, the compound or composition provided herein can be used For the treatment, prevention or improvement of one or more symptoms of intrahepatic or extrahepatic bile stagnation, including but not limited to cholestatic arteritis, obstetric bile stagnation, neonatal bile stagnation, drug-induced < bile stagnation, due to hepatitis c Bile stagnation and chronic bile stagnation liver disease caused by infection, such as primary biliary sclerosis (PBC) and primary sclerosis Cholangitis (PSC). Further provided by the present invention is a method of treating obesity and treating obesity complications by administering a compound or composition of the present invention. 85585 -24- 200307684 Also intended to be included herein as a combination Therapy, using one or more compounds or compositions provided herein or a pharmaceutically acceptable derivative thereof, and using one or more of the following: antihyperlipidemic agents, plasma HDL-raising agents, antihypercholesterolemia agents Cholesterol biosynthesis inhibitors (such as HMGCoA reductase inhibitors such as lovastatin, simvastatin, pravastatin, fluvastatin ), Atovastatin and rivastatin), Si-Coenzyme A: Cholesterol Aminotransferase (ACAT) inhibitor, Probucol, Raloxib Raloxifene, nicotinic acid, nicotinamide, cholesterol absorption inhibitors, bile acid sequestrants (such as anion exchange resins or quaternary amines (such as cholestyramine or cholestyramine) (Colestipol))), low-density lipoprotein receptor hairpins, clofibrate, fenofibrate, benzofibrate, benzofibrate (cipofibrate), gemfibrizol, vitamin B6, vitamins & 2, antioxidant vitamins, chill-blockers, antidiabetic agents, angiotensin II antagonists, angiotensin converting enzyme inhibitors, platelet aggregation inhibition Agent, fibrinogen receptor antagonist, LXR alpha or / 3 activator, antagonist or partial activator, aspirin or fibric acid derivative. The compound or composition provided herein or a pharmaceutically acceptable derivative thereof is administered at the same time as, before, or after the administration of one or more of the aforementioned agents. Also provided are pharmaceutical compositions comprising a compound provided herein and one or more of the aforementioned agents. In carrying out such methods, an effective amount of a compound or composition containing a therapeutically effective concentration of the compound is formulated for systemic delivery, including parenteral, oral or intravenous delivery, or for regional or Topical application, 85585 -25- 200307684 to treat nuclear receptors including farnesin x receptors and / or orphan nuclear receptor-mediated I diseases or conditions, or where implicated nuclear receptor activity includes farnesin x receptors Diseases and conditions of the body and / or orphan nuclear receptor activity, including but not limited to hypercholesterolemia, hyperproteinemia, hypertriglyceridemia, lipometabolic disorders, blood glucose, diabetes, dyslipidemia, atherosclerosis Tumor sclerosis, gallstone disease, acne vulgaris, acne-like skin symptoms, diabetes, Parkinson's disease, cancer, Alzheimer's disease, inflammation, immunological disorders, lipid disorders, obesity, characterized by disruption of epidermal barrier function Symptoms, hyperlipidemia, bile stagnation, peripheral occlusive disease, hemorrhagic stroke, epidermal or mucosal I disturbance of differentiation or hyperproliferative symptoms or cardiac and vascular disorders, administration Individuals showing signs of these diseases or conditions. This amount is effective to ameliorate or eliminate one or more symptoms of the disease or disorder. Provided-a product containing packaging material, a compound provided herein, or an oral product or a pharmaceutically acceptable derivative thereof, which is effective in modulating nuclear receptors including farnesin X receptors and / or orphans Nuclear receptor activity, or treatment, prevention, or improvement of nuclear receptors including tweed receptors and / or orphan nuclear receptors, "disease or condition, or in which nuclear receptor activity is implicated includes farnesin-like x stylistic and And / or disease or condition of orphan nuclear receptor activity—in the packaging material, and a sign indicating that the compound or composition or a scientifically acceptable derivative thereof is used to modulate nuclear receptors Including the activity of farnesin-like W-body and / or orphan nuclear receptors, or to treat, treat or improve diseases or diseases mediated by nuclear receptors including farnesin-like X receptors and / or orphan nuclear receptors, or One or more symptoms of a disease or disorder in which nuclear receptor activity is implicated includes farnesin x receptor and / or orphan nuclear styloid activity. 85585 -26- 200307684 Detailed description of the invention A. Definitions, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this invention belongs. All patents, applications, published applications, and other bulletins' are hereby incorporated by reference in their entirety. In the case where there is more than one definition of a term in this text, the one in this paragraph is dominant unless otherwise mentioned. The nuclear receptor used in this text is a member of the regulatory protein superfamily, which is for example Receptors for steroids, retinoids, vitamins and thyroid hormones. These proteins are bound to their target genes, cis-acting elements in the promoter + and modulate gene expression, and respond to ligands for their use. Nuclear receptors are classified based on their DNA-binding properties. For example, the combination of corticoids, hormonal hormones, androgens, luteinizing agents, and mineral corticosteroid dimers to hormone response elements that invert repetitive tissues. Another example is stylistics, including retinoic acid, thyroid hormones. , Vitamin h, fatty acid / peroxisome proliferators, and activators activated by berberin, are bound to HRE by heterodimers with a common counterpart, human visual pigment x receptor (RXR). Among the receptors mentioned later, they are farnesin-like receptors. The orphan nuclear acceptor system used herein is a gene product, which specifically represents the structural characteristics of nuclear receptors, and has not been identified without any prior knowledge of its association with inferred ligands, and / or its natural ligands. The bit system is unknown. In this definition, the orphan nuclear acceptor system includes, but is not limited to, farnesin-like receptors, liver X stylistics (LXR α & / 5), retinoid x receptors (RXR α, stone & phantom, and peroxygen). 85585 -27- 200307684 activator of proteasome proliferator activator (PPAR α, zhao & τ〇 (see Giguere, Endocrinology (1999), Vol. 20, No. 5: pages 689-725). As used herein, farnesin x receptors refer to all mammalian forms of such receptors, including, for example, alternatives to conjugating isomeric recombinants to naturally occurring isomeric recombinants (see, for example, Huber et al. (2002 ), Vol. 290, pp. 35-43). Representative species of farnesin X receptor species include, but are not limited to, rats (Gene Bank Registration Number NM-021745), mice (Gene Bank Registration Number) NM—009108) and human (gene bank registration number __〇〇5123). 0 Pharmaceutically acceptable derivatives of the compounds used herein include their salts, esters, enol ethers, associations Alcohol esters, acetals, ketals, orthoesters, hemiacetals, hemiketals, acids, bases, Solvates, hydrates or prodrugs. Such derivatives can be easily made by those skilled in the art using known methods for such derivatization. The compounds produced can be administered to animals or humans , Without substantial toxic effects, and whether it is medicinally active or a prodrug. Pharmaceutically acceptable salts include, but are not limited to, amine salts: such as but not limited to N, N, -di-ylethylenediamine, chlorine Procaine, choline, ammonia, diethanolamine and other hydroxyalkylamines, ethylenediamine, N-methylglucamine, procaine, N-benzylphenylethylamine, chlorobenzyl _2_Tetrahydropyrha_1L-based methylbenzimidazole, diethylamine and other alkylamines, hexahydropyridine, and ginseng (I methyl version of methane; alkali metal salts, such as but not limited to lithium, Potassium and sodium; soil test metal salts such as but not limited to barium, magnesium and magnesium; transition metal salts such as kernel not limited to zinc, and other metal salts such as but not limited to sodium hydrogen phosphate and "sodium hydrogen phosphate, and also Including but not limited to salts of mineral acids, such as but not limited to present acids I and & I salts, and salts of organic acids, such as but not In acetate 85585 -28- 200307684, lactate, malate, tartrate, citric acid, ascorbate, succinate, butyrate, valerate and fumarate. Pharmaceutically acceptable Esters, including, but not limited to, acidic groups such as alkyl, fluorenyl, block, aryl, heteroaryl, aralkyl, heteroaralkyl, cycloalkyl, and heterocyclic groups, including but Not limited to carboxylic acid, phosphoric acid, phosphinic acid, sulfonic acid, phosphinic acid, and dikisyl rotane. Pharmaceutically acceptable allyl ethers include, but are not limited to, derivatives of formula C = C (OR), where R is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, cycloalkyl, or heterocyclyl. Pharmaceutically acceptable enol esters, including but not limited to derivatives of the formula c = c (〇c (〇) R), where R is fluorenyl, alkyl, fluorenyl, block, aryl, heteroaryl , Aralkyl, heteroaralkyl, cycloalkyl, or heterocyclyl. A pharmaceutically acceptable solvate and hydrate is a compound with one or more solvents or water molecules, or 1 to about 100, or 1 to about 10, or one to about 2, 3, or 4 solvents or water molecules Of the complex. As used herein, treatment refers to any manner in which one or more symptoms of a disease or condition is ameliorated or advantageously altered. Treatment also encompasses any medicinal use of the compositions herein, such as the treatment of a disease or condition mediated by a nuclear receptor, or a disease or condition in which the activity of the involved nuclear receptor includes farnesin-like receptor or orphan nuclear receptor activity. . As used herein, the improvement of symptoms of atopic disease by administering a specific compound or pharmaceutical composition refers to any reduction, whether permanent or temporary, continuous or temporary, which can be attributed to the administration of the composition or otherwise Associated. 1C: 50, as used herein, refers to the amount, concentration, or dose of 50% inhibition of the maximum response achieved by a particular test compound, such as in a test 85585 -29- 200307684 measuring 'modulation nuclear response' The body includes farnesin-like X receptor activity. As used herein, EC: 50 refers to the dose, concentration, or amount of a particular test compound that induces a dose-dependent response under 50% of the maximum performance of a particular response induced, induced, or enhanced by a particular test compound. . As used herein, a prodrug is a compound that, when administered in vivo, is biologically metabolized by one or more steps or procedures, or is converted into a biologically, pharmaceutically or therapeutically active form of the compound. To produce a prodrug, the pharmaceutically active compound is modified so that the active compound will be regenerated by a metabolic program. Prodrugs can be designed to alter the metabolic stability or delivery characteristics of a drug, to mask side effects or toxicity, to improve the taste of a drug, or to alter other characteristics or properties of a drug. Due to the in-vivo knowledge of pharmacodynamic processes and drug metabolism, once a medically active compound is known, those skilled in the art can design compound precursor drugs (see, for example, Nogrady (1985) 着 翔 允 荸 至 # 允Xue Honghong, Oxford University Press, New York, pp. 388-392). When the compounds described herein contain fluorene double bonds or other centers of geometric asymmetry, and unless otherwise specified, these compounds are intended to include 与 and 2 汆 Hing structures. Likewise, all tautomeric forms are intended to be included. It should be understood that the compounds provided herein may contain palm centers. This opponent center can be either ⑻ or ⑻ configured, or it can be a mixture. Thus, the compounds provided herein may be para-isomerically pure, or may be stereoisomeric or diastereomeric mixtures. In the case of amino acid residues, such residues may be in either K or D · form. 85585 200307684 about naturally occurring amino acid residues, and the heart system is L. When not specified, this residue is in the L form. The term "sense amino acid" is used herein to refer to ... an amino acid, which is racemic, or whether it is a D- or L-configuration. The name immediately before the amino acid name, for example ^ dAla, dSer, dVal, etc.) refers to the D-isomer of amino acid. The name immediately before the name of amino acid "dl ,, (eg * dlpip) refers to the dagger and isomerization of amino acid A mixture of things. It should be clear that the compounds provided herein can perform epimerization in vivo on the palm center. Because of &, the skilled artist will know that the drug is administered in its (R) form. For compounds that undergo epimerization in vivo, it is equivalent to the compound being administered in the form of hydrazone. = Study activity ㈩ and (_), ⑻- and (S)-, or (D)-and (L)-isomers, which can be formed using palmarity synthesis units or palmarity trials, or use conventional techniques such as Resolved by HPLC. Essentially pure used in this text means that it is sufficiently homogeneous to appear free of immediately detectable impurities when measured by a standard knife analysis method, such as by asking the artist to evaluate this kind of heat Purity of thin layer chromatography (tlc), gel electrophoresis, high performance liquid chromatography (HPLC) and mass spectrometry (MS), or pure enough so that further purification will not measure physical and chemical properties Changes, such as the enzymes and biological activity of matter. Methods for purifying compounds for producing substantially chemically purified compounds are known to those skilled in the art. However, a substantially chemically pure compound can be a mixture of stereoisomers. In such cases, further purification may increase the specific activity of the compound. The alkyl, alkenyl and alkynyl carbon chains used herein, if not specified, contain 1 to 20 carbons or 2 to 16 carbons, and are straight or branched. Alkenyl carbon chains of 2 to 20 carbons, in some specific embodiments, contain 1 to 8 85585 -31-200307684 double bonds, and fluorenyl carbon chains of 2 to 16 carbons, in some specific embodiments Contains 1 to 5 double bonds. An alkynyl carbon chain of 2 to 20 carbons, in some specific embodiments, contains 1 to 8 reference bonds, and an alkynyl carbon chain of 2 to 16 carbons, in some specific examples, contains 1 to 5 reference keys. Examples of alkyl, alkenyl, and bulk groups herein include, but are not limited to, methyl, ethyl, propyl, isopropyl, isobutyl, n-butyl, second-butyl, and third-butyl Base, isopentyl, neopentyl, tert-pentyl, isohexyl, allyl (propionyl) and propargyl (propynyl). As used herein, lower alkyl, lower alkenyl and lower alkynyl refer to carbon chains having from about 1 or about 2 carbons up to about 6 carbons. As used herein, "alk (en) (alkynyl)" refers to an alkyl group containing at least one double bond and at least one reference bond. "Cycloalkyl" as used herein refers to a saturated mono- or Polycyclic ring systems, in some embodiments 3 to 10 fluorene atoms, in other embodiments 3 to 6 interfering atoms; cycloalkenyl and cycloalkynyl refer to mono- or polycyclic The 'ring system' individually includes at least one double bond and at least one reference bond. Cycloalkenyl and cycloalkynyl may, in certain embodiments, contain 3 to 10 carbon atoms, where cycloalkenyl is in other specific embodiments Contains 4 to 7 carbon atoms, while cycloalkynyl contains 8 to 10 carbon atoms in other specific embodiments. The ring system of alkyl, dilute and cycloalkynyl can consist of one ring or two or more rings. The ring can be fused, bridged or spliced together. &Quot; Cyclo (alkene) (alkyne :) group " refers to a cycloalkyl group containing at least one double bond and at least one reference bond. As used herein, "aryl" refers to an aromatic monocyclic or polycyclic group containing 6 to 19 carbon atoms. Aryl includes, but is not limited to, for example, unsubstituted or substituted f groups, unsubstituted A substituted or substituted phenyl group and an unsubstituted or substituted fluorenyl group. 85585 -32- 200307684 As used herein, "heteroaryl" refers to a monocyclic or polycyclic aromatic ring system In some specific embodiments, it is about 5 to about 15 members, in which one or more of the ring systems, in a specific embodiment, 1 to 3 atomic systems are heteroatoms, meaning that they are not Elements of carbon, including but not limited to nitrogen, oxygen, or sulfur. Heteroaryl groups may be fused to the benzene ring as appropriate. Heteroaryl groups include, but are not limited to, furyl, imidazolyl, pyrimidinyl, tetrazolyl, pyrenyl, Pyridyl, pyrrolyl, oxazolyl, isoxazolyl, oxazolyl, isoxazolyl, triazolyl, quinolinyl, and iso-Pquelinyl. As used herein, "heteroaryl salts," A group is a heteroaryl group that is positively charged on one or more heteroatoms. "Heterocyclyl" as used herein refers to a monocyclic or polycyclic non-aromatic ring system, which is 3 to 10 members in one embodiment, and 4 to 7 in another embodiment 5 to 6 members in further specific embodiments, in which one or more of the ring systems, in some specific embodiments, 1 to 3 atomic systems are heteroatoms, meaning elements other than carbon Including, but not limited to, nitrogen, oxygen, or sulfur. In a specific embodiment in which the heteroatom is nitrogen, the nitrogen is optionally an alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, cycloalkyl, heterocyclic group , Cycloalkylalkyl, heterocyclylalkyl, fluorenyl, guanidino, or the nitrogen may be quaternized to form an ammonium group, wherein the substituents are selected as described above. As used herein, "aralkyl" refers to an alkyl group in which one of the hydrogen atoms of an alkyl group is replaced with an aryl group. As used herein, "heteroaralkyl" refers to an alkyl group in which one of the hydrogen atoms of the alkyl group is replaced by a heteroaryl group. 85585 -33- 200307684 4 " halo ", " Halogen " or " halide, which means f, α, Br or I. As used herein, a privatized or pseudofluorinated group is a group that behaves substantially like a halide. Such compounds can be used and treated in the same manner as the compounds. Pseudo-chemical compounds include, but are not limited to, cyanide, cyanate, thiocyanate, selenocyanate, trifluoromethoxy, and azide. As used herein, "dentate alkyl" refers to an alkyl group in which one or more hydrogen atoms have been replaced by a dentine. Such groups include, but are not limited to, chloromethyl, trifluoromethyl, and chloro-2-lactylethyl. As used herein, "from alkoxy" refers to R0_, where the rule is _alkyl. As used herein, "sulfenyl" or "sulfinyl" refers to _S (〇) _. As used herein, "sulfofluorenyl, or" thiosulfanyl "refers to _S (0) 2_. As used herein," sulfonyl "refers to -S (0) 20-. As used herein, " halosulfonyl " refers to -S (0) 2_R, where R is a halogen group, preferably a fluoro group. As used herein, "acid group" refers to a divalent radical _c (〇) 〇_. As used herein, "aminocarbonyl" refers to -c (0) NH2. "Alkylaminocarbonyl" as used herein refers to -c (0) NHR, where R is an alkyl group, including a lower alkyl group. "Dialkylaminocarbonyl group," as used herein, refers to -C (0) NR; R, wherein R 'and r are independently alkyl groups, including lower alkyl groups; " carboxamide' refers to a group of the formula -NR'COR, wherein alkyl groups independently of the ruler system, Including lower alkyl. As used herein, "diarylaminocarbonyl" refers to ((〇) _ &, where R and R 'are independently selected from aryl, including lower aryl, such as benzene base.

As used herein, "aralkylaminocarbonyl" refers to ((0) ^^, where one of R 85585 -34- 200307684 and R 'is an aryl group, including a low aryl group, such as phenyl, and The other one of R and R is a group, including a low-carbon group. As used herein, "arylaminocarbonyl" refers to _C (0) NHR, where r is an aryl group, including a lower aryl group, such as Phenyl. "Hydroxycarbonyl" as used herein refers to -COOH. "Alkoxycarbonyl" as used herein refers to -C (0) OR, where R is an alkyl group, including a lower alkyl group. As used herein, "1f aryloxycarbonyl" refers to -C (0) OR, where R is an aryl group, including a lower carbon aryl group, such as phenyl. "Alkoxy" and "" Alkylthio refers to R0- and RS_, where R is alkyl, including lower alkyl. As used herein, "aryloxy" and "arylthio" refer to R0_ and RS_ , Where R is an aryl group, including a low-carbon aryl group, such as phenyl group. As used herein, the term "pi" means straight chain, branched or cyclic, and in some embodiments, it is straight chain or Branched divalent aliphatic hydrocarbon group In one embodiment, it has 1 to about 20 carbon atoms, and in another embodiment, it has 1 to 12 carbon atoms. In a further embodiment, the alkylene group includes a lower carbon alkylene group. There may be Optionally insert one or more oxygen, sulphur along the alkylene group 'including S (O) and S (O) 2 groups' or optionally substituted nitrogen atoms, including with -N + RR- groups' Wherein the nitrogen substituent is alkyl, aryl, aralkyl, heteroaryl, heteroaralkyl or COR ', where R' is alkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, -OY or -NYY, where γ is hydrogen, alkyl, aryl, heteroaryl, cycloalkyl, or heterocyclyl. The alkylene group includes, but is not limited to, methylene (_CH2_), and ethylidene (-( ¾ (¾-), propylene (_ (CH2 h-), methylenedioxy (_〇-Ch2 _〇_) 85585 -35- 200307684 and ethylenedioxy (-0- (CH2) 2_0 -). ,, a lower alkylene group, the term refers to a secondary alkyl group having J to 6 carbons. In certain embodiments, an alkylene group is a lower carbon alkylene group including 1 to 3 Secondary atom of carbon atom. As used herein, "nitrogenated alkyl group" refers to-(CRR) n-NR -(CRR) m-, where η and m are each independently an integer of 0 to 4. As used herein, " oxyalkylene " refers to-(CRR) n-0- (CRR) m-, where Each independently is an integer of 0 to 4. As used herein, "thioalkylene" means-(CRR) n_S- (CRR) m-,-(CRRVSPXCRRX ^, and _ (CRR) nS (0) 2-( CRR) m-, where η and m are each independently an integer of 0 to 4. "Sinylene" as used herein refers to a straight chain, branched or cyclic, and in a specific embodiment is a linear or branched divalent aliphatic hydrocarbon group. In some specific embodiments In the embodiment, it has 2 to about 20 carbon atoms and at least one double bond, in other specific embodiments, 1 to 12 carbons. In other specific embodiments, the hypofluorenyl group includes a low-carbon alkenylene group. There may be cases Insert one or more oxygen, sulfur, or optionally substituted nitrogen atoms along the fluorenyl group, where the nitrogen substituent is an alkyl group. The fluorenyl group includes, but is not limited to, -CH = CH-CH = CH- and -CH = CH_CH2-. "Low-carbonene alkenylπ — The word refers to a hypofluorenyl group having 2 to 6 carbons. In certain embodiments, the alkenylene group is a lower carbon alkenyl group, including a hypofluorenyl group of 3 to 4 carbon atoms. As used herein, a "hypoalkynyl" refers to a straight-chain, branched, or cyclic, and in some embodiments, a straight-chain or branched divalent aliphatic hydrocarbon group. In a specific embodiment , Has 2 to about 20 carbon atoms and at least one reference bond, in another specific embodiment is 1 to 12 carbons. In a further specific embodiment, the alkynyl group includes a lower alkynylene. It may be optional In this case, one or more oxygen, sulfur, or optionally substituted nitrogen atoms are inserted along the alkynyl group, wherein the nitrogen substituent 85585 -36- 200307684 is an alkyl group. The alkynyl group includes, but is not limited to, -CeC-CeC-, -CeC- and -CeC-CH2-. The term `` lower alkynylene '' refers to a hypoalkynyl group having 2 to 6 carbons. In certain embodiments, the alkynyl group is a lower alkynyl group Hydrazone, including a subordinate radical of 3 to 4 carbon atoms. As used herein, "alkylene (fluorene) (alkynyl)" refers to a straight chain, branched, or cyclic 'in some embodiments, it is A linear or branched divalent aliphatic hydrocarbon group, in a specific embodiment, has 2 to about 20 carbon atoms and at least one reference bond and at least one double bond; in another In the specific embodiment, it is 1 to 12 carbons. In other specific embodiments, the alkynyl (alkynyl) group includes a low-carbon alkynyl (alkyn) (alkynyl) group. The alkynyl group may be optionally inserted along the alkynyl group. One or more oxygen, sulfur, or optionally substituted nitrogen atoms, where the nitrogen substituent is an alkyl group. Hypoalkylene (hydrazone) (alkynyl) groups include, but are not limited to, -C = C- (CH2) n-CEC- Where η is 1 or 2. " Low-carbon secondary (ene) (block) group, the term refers to an alkylene (fluorene) (alkynyl) group having up to 6 carbons. In some specific embodiments An alkylene (alkynyl) group has about 4 carbon atoms. As used herein, "subcycloalkyl" refers to a divalent saturated mono- or polycyclic ring system, which in some embodiments is 3 to 10 carbon atoms, in other specific embodiments 3 to 6 carbon atoms; hypocycloalkenyl and hypocycloalkynyl refer to a divalent mono- or polycyclic ring system, each of which contains at least one double bond and At least one parameter key. The hypocyclofluorenyl group and hypocycloalkynyl group may contain 3 to 10 carbon atoms in certain embodiments, wherein the cycloalkenyl group contains 4 to 7 old atoms in certain embodiments, and the secondary ring Alkynyl, in certain embodiments, contains 8 to 10 complete atoms. The ring system of the secondary ring alkylene group, the secondary cycloalkenyl group and the secondary cycloalkyl group may be composed of one ring or two or more rings, and the rings may be joined together in a fused, bridged or spiro connection manner. ", A cycloalkane (fluorene) (alkynyl) group" means a secondary cycloalkyl group containing at least 85585 -37- 200307684 a double bond and at least one reference bond.

Low carbon subaryl. In other specific embodiments, the subaryl group includes a perylene group including, but not limited to, 1,2,1,3-, and 1,4-phenylene. '' Low-carbon subarylπ — The word refers to a subaryl having 6 carbons. As used herein, "sub-heteroaryl" refers to a bivalent monocyclic or polycyclic aromatic ring system. In a specific embodiment, about 5 to about 15 atoms are in the ring, where in this ring system One or more of them, in some specific embodiments, are 3 to 3 atoms are heteroatoms, meaning elements other than carbon, including but not limited to nitrogen, oxygen, or sulfur. The term π-lower carbon heteroaryl " refers to a secondary heteroaryl having 5 or 6 atoms in the ring. As used herein, a "sub-heterocyclyl" refers to a divalent monocyclic or polycyclic non-aromatic ring system, in some embodiments from 3 to 10 members, and in a specific embodiment, 4 to 7 members, 5 to 6 members in another specific embodiment, in which one or more of the ring systems, including 1 to 3 atomic systems are heteroatoms, meaning elements other than carbon, Including but not limited to nitrogen, oxygen, or sulfur. As used herein, "substituted alkyl", "substituted fluorenyl", ", substituted alkynyl", ", substituted ring "Alkyl", π substituted cycloalkenyl " ,, substituted cycloalkynyl, ", substituted heteroaryl ", ", substituted heteroaryl ", ", substituted Heterocyclyl ,,,,, substituted subalkyl ", " substituted subfluorenyl ,,,,, substituted subdecyl ,,,, " substituted subcyclic alkyl group 1f, "; Substituted subcyclofluorenyl ", " Substituted subcyclopentyl ", Substituted subaryl ", " 85585 -38- 200307684 Substituted subheteroaryl " `` Substituted secondary heterocyclyl '' refers to alkyl, fluorenyl, alkynyl, cycloalkyl, cyclofluorenyl, cycloalkynyl, aryl, heteroaryl, heterocyclyl, hypoalkyl, Alkenyl, alkynyl, cycloalkyl, cycloalkynyl, cycloalkynyl, aryl, heteroaryl, and heterocyclic groups, which are substituted by one or more substituents, in some The specific embodiment is one, two, three or four substituents, wherein the substituents are as defined herein, and in a specific embodiment is selected from Q1. As used herein, "alkenylene" refers to divalent Basic solids, such as = CR, R ", are connected to one atom of another group to form a double bond. The alkylene group includes, but is not limited to, methylene (= CH2) and ethylene (= CHCH3). As used herein, "arylalkylidene '" refers to an alkylene group in which any one of R, or R " is an aryl group. "Cycloalkylene" is one in which R and R "are connected to form a carbocyclic ring." Heterocyclic group is in which at least one of R1 and R "contains a heteroatom in this chain, and R, and Rn are connected Instead, a heterocycle is formed. As used herein, " fluorenamine " refers to a divalent group of seven (〇) ^ _. &Quot; thiocarbamide refers to a monovalent group -C (S) NH-. &Quot; The "group" refers to a divalent group _ 0C (0) NH-. The "thioamino" group refers to a divalent group _sc (〇) NH_. ", Dithiocarbamido" refers to a divalent group. ,, ureido, refers to a divalent group · HNC (0) NH-. 11 thioureido "refers to a divalent group ννη ·. "Amineurea" as used in this specification refers to -NHC (〇) NHNH_. "Hydrazine formate" refers to a hydrazone group-0C (0) NHNH-. ,, isothiocarbazate, refers to the divalent group -SC (0) NHNH-. "Thithiocarbamate" refers to the divalent group _〇c⑸nhnh_.% Fluorenyl hydrazine "refers to the divalent group name 02NHNH_, and hydrazine" refers to the divalent group -C ( 0) NHNH-. &Quot; Azo " refers to the divalent group _N = N_. &Quot; Hydrazine, 85855 -39- 200307684 refers to the divalent group -NH-NH-. In any particular substitution In cases where the number of groups is not specified (such as a haloalkyl group), one or more substituents may be present. For example, a "haloalkyl group" may include one or more of the same or different halogens. The following is used as another As an example, "-3alkoxyphenyl" may include one or more alkoxy groups containing one, two or three carbons which may be the same or different. As used herein, the abbreviations for any protecting groups, amino acids, and other compounds, unless otherwise specified, are based on their common law, approved abbreviations, or the IUPAC-IUB Committee's biochemical nomenclature (see ( 1972) 5 Magic: 942-944). When used herein, the following terms have their accepted meanings in the chemical literature.

AcOH acetic acid CDI carbodiimide CHC13 chloroform cone concentrated DBU 1,8-diazabicyclo [5.4.0] undec-7-ene DCM dichloromethane DDQ 2,3-dichloro-5,6-dicyano -1,4-benzoquinone DIEA diisopropylethylamine DMAP dimethylaminopyridine DME 1,2-dimethoxyethane DMF N, N-dimethylformamidine DMSO dimethylarsine 85585 -40 -200307684 ELSD Evaporative Light Scattering Detector EtOAc Ethyl Acetate EtOH Ethanol (100%) Et〗 0 Ethyl HBTU 1-H_benzotrimethylene, bis (dimethylamino) methylene] -hexafluorophosphoric acid (1-), 3-oxide hexafluorophosphate 0- (benzotriazole small group) -N, N, Nf, M tetramethylfluorene Hex hexane h2 so4 LDA sulfate Lithium di (isopropyl) amine MeCN Acetonitrile MeOH Methanol NaBH3 CN Sodium cyanoborohydride Pd / C Zingba / reactive TEA triethylamine THF tetrahydrofuran TFA trifluoroacetic acid B. Preferred embodiments of the compounds of the present invention The present invention provides for the use of And methods to modulate nuclear receptor activity. In particular, compounds are provided for use in compositions and methods to modulate farnesin-like X receptors) and / or orphan nuclear receptors. In certain embodiments, the compound of the present invention, as described in the summary of the present invention, is a compound of formula (I) or formula (II): -41- 85585 200307684

Where R1 is optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, _C (0) R18, -C (0) 0R14, -C (0) N (R15) R16 or -C (0) N (R17) N (Ri5) R16; where R14, R15, R16, R17, and R18 are each as defined in the Summary of the Invention above; and R2-R9 are each as defined in the Summary of the Invention above . In another specific embodiment, R1 is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heterocyclic Aryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, -〇! ^ 14, Qiu 1115) 1116 ,-&^; ^ 17 stomach] ^ # 6 ^ C (0) R18, -C (0) 0R ", (⑼ ⑼1, ^ where R18 is as described in the content of the invention above, and wherein 14, R15, R16 and R17 are selected from among the following: or 14, Rl5, & 16 and "7 are each independently hydrogen, the substituted tiger group is replaced, the diluted base is replaced as appropriate, and the Substituted decyl group,% substituted group in case I, n ^^ 85585 -42- 200307684 substituted heterocyclic group, optionally substituted aryl group, optionally substituted heteroaryl group, optionally substituted group Aralkyl or optionally substituted heteroaryl groups; or ⑻R15 and R16 and the nitrogen atom to which they are attached together to form a heterocyclic ring optionally substituted or optionally substituted Aryl ring, and Rl4 and R1 7 are selected as in (a) above; and R2 is hydrogen or optionally substituted alkyl, or R1 and R2 and the atom to which they are connected form a substituted as appropriate Cycloalkyl, optionally substituted heterocyclyl, or optionally substituted heteroaryl ring. In another specific embodiment, Ri is optionally substituted alkynyl, optionally substituted aryl , Optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted arylplate radical, optionally substituted heteroarylalkyl, -〇1114 ,-: ^ (1115 boundary 16, -N (R17) N (R15) R16, -C (0) R18, -C (0) 0R14, -C (0) N (R15) R16, or -C (0) N (R17) N (R15) R16; where Ris is as described in the summary above, and where R14, R15, r16, and r17 are selected from ⑻ or 如 as follows: ⑻R14, R15, R16, and R17 are each independent Hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted Aryl, as appropriate Substituted heteroaryl, optionally substituted aralkyl, or optionally substituted aromatic aryl; or (b) R15 and R16 together with the nitrogen atom to which they are attached form a optionally substituted heteroaryl Ring, and R14 and R17 are selected as in ⑻ above, and R2 is hydrogen or optionally substituted alkyl; or R1 and r2 and the atom to which they are attached together form a optionally substituted heterocyclyl ring In another specific embodiment, R1 is selected from the group consisting of optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl,-(C〇) 〇- (视 85585- 43-200307684 in the case of substituted alkyl), -C (0) OH or -CCCONCR15) Ri6, where Ri5 and Ri6 are as described in the above summary. In another specific embodiment, R15 is optionally substituted alkyl. In another specific embodiment, Ri5 is alkyl. In another embodiment, R16 is hydrogen. In another embodiment, R1 is-(C0) 0- (optionally substituted alkyl), -C (0) 0H or -C (0) N (H) R15, where R15 is optional Substituted alkyl. In another specific embodiment, R1 is isopropyl, 4-nitrophenyl, 3-thienyl, 1-phenyl-1-ethyl. In another specific embodiment, Ri is _c (o) och2ch3, sunny c (o) och3, -c (o) oc (ch3) 2h, -c (o) oh, -c (o) och2ch2ch3, -C (0) N (H) CH3 or -C (0) N (H) CH2CH3. In another embodiment, R2 is hydrogen or optionally substituted alkyl. In another embodiment, R2 is hydrogen or alkyl. In another embodiment, R2 is hydrogen. In another specific embodiment, R3 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted Heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl,-(: (0) 1144,- (: (0) 0111 (), 402111 (), -C ^ NCR11) R'0 '-C (0) N (Rii) N (R12) Ri. ^ (R11) 0 (0) ^ 0'- N (Rn) -C ^ NCR12) R! 0 ^ -N (Ru) C (〇) N (R12) N (R13) R10 '-NCR11 ^ (OPR10' -P (0) OR10 or -P (〇) (〇R19) 〇Ri〇; wherein Ri0, Rii, R12, Rl3 & R19 is selected from the following ⑻ or (b) ... (a) Rl1, R1 2, Rl3 and Rl9 are each independently Hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted decyl, optionally substituted cycloalkyl, optionally substituted 85585 • 44- 200307684 heterocyclic group, optionally Optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, or optionally substituted heteroaralkyl; and R10 is Substituted entertainment: base, optionally substituted amidino, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, Optionally substituted heteroaryl, optionally substituted aralkyl, or optionally substituted heteroaralkyl; or (b) R10 and R11, and / or R1G and R12, and / or R10 and R13, And / or R1G and R19, and / or R11 and R12, and / or R12 and R13, together with the atoms to which they are attached, form optionally substituted heterocycles or optionally substituted heteroaryl rings; and others R10, R11, R12, R13, and R19 are selected from 如 as above; and 为 4 is optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, and optionally Substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, or optionally substituted heteroaralkyl. In another specific embodiment , R3 is optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted Heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, -C (〇) R44, -C (0) 0R1 (), -S02R10, -C (0) N (Rn) R1 (), -C (0) N (R ") N (R12) R10, -NCR11) C (0) Rl 0 ^- NCR11) C (0) ml 2 ° '^ (R11) C (〇MRl 2 MR13 °, -N (Rn) C (0) OR10, -P (0) 〇R10 or -P (〇) (〇R19) ORl0; where Rl0, RU, R12, R13, and R19 are selected from ⑻ or (b) as follows: ⑻Rl 1, Rl 2, R13, and R19 are each independently hydrogen, optionally substituted alkyl, or Substituted alkenyl, optionally substituted decyl, optionally substituted cyclohexyl 85585-45-200307684, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted aryl Heteroaryl, optionally substituted aralkyl, or optionally substituted heteroaralkyl; and r1g is optionally substituted alkyl, optionally substituted fluorenyl, optionally substituted decyl, Substituted as the case may be, so the base is optionally substituted heterocyclyl, optionally substituted by aryl, Substituted heteroaryl, optionally substituted aralkyl, or optionally substituted heteroaralkyl; or (b) R1G and R11, and / or R1G and R12, and / or ^ and 1113, and / or R1G and R19, and / or R11 and R12, and / or Rl2 and Rl3, together with the atoms to which they are attached, form optionally substituted heterocycles or optionally substituted heteroaryl rings; and other R10, R11 , R12, R13, and R19 are selected as in (a) above; and R44 is optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted Heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, or optionally substituted heteroaralkyl. In another specific embodiment, R3 is optionally substituted decyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted Heterocyclyl, optionally substituted heteroaralkyl, -0: 〇) 1 ^, < (〇) 〇1146, -〇２ 仏 10, < (〇) > 1 (1111) 1147, C (0) N (Rn) N (R12) R10--NCR11) 0 (0) ^ 0 '-N (Ru) C (0) N (R12) R10' -N (Rn) C (0) N (R12) N (R13) R10 > -NCR11) 0 (0) 0 ^ 0 ^ -P (0) OR10 or -P (0) (OR19) OR10; where R47, Rio, Rii, R12, R13, and R19 Choose from ⑻ or (b) as follows: ⑻Rii, r! 2, Ri3, and Ri9 are each independently hydrogen, optionally substituted alkynyl, optionally substituted fluorenyl, and optionally substituted alkynyl , Optionally substituted cycloalkyl, optionally substituted heterocycle 85585 -46- 200307684, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, or Optionally substituted heteroaralkyl; r47 is optionally substituted fluorenyl, optionally substituted alkynyl, optionally substituted heterocyclyl, optionally Optionally substituted heteroaryl or optionally substituted heteroaralkyl; and R1 G is optionally substituted alkyl, optionally substituted fluorenyl, optionally substituted alkynyl, optionally substituted Cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, or optionally substituted heteroaralkyl • , Or (b) R1G and R11, and / or R10 and R12, and / or R10 and R13, and / or R1G and R19, and / or R11 and R12, and / or R12 and R13, and / or R47 and R11 Together with the atoms to which they are connected to form optionally substituted heterocycles or optionally substituted heteroaryl rings; and the other R47, R1G, R11, R12, R13 and R19 are selected as above; R45 is optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, optionally substituted aralkyl, or optionally substituted Heteroarylalkyl; and R46 is optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted ring Group, the optionally substituted heterocyclic group, the optionally substituted aryl, optionally substituted aryl or heteroaryl of optionally substituted heteroaryl group of. In another specific embodiment, R3 is hydrogen or -X-R10, where X is < (0)-, -C (0) 0-, -S02 _ or-(^ (Ο) Ν (ΙΙ11) -; Wherein R10 and R11 are as described above. In another specific embodiment, R10 is optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alkyl, or optionally substituted Arylalkyl. In another specific embodiment, when Ri0 is substituted, it is halo 85585 -47- 200307684, pseudoalkyl, alkyl, alkoxy, hypoalkylenedioxy, haloalkane Group, nitro, cyano, -C (0) 0-alkyl, aryl, -S02F or haloalkoxy. In another specific embodiment, R11 is hydrogen or optionally substituted alkyl In another specific embodiment, R11 is hydrogen or alkyl. In another specific embodiment, R11 is hydrogen. In another specific embodiment, R3 is -C (OH is substituted as appropriate) Aryl), -c (o)-(optionally substituted heteroaryl), -c (o > (optionally substituted alkyl), hydrogen, -S02- (optionally substituted aryl ), -C (0) (CH2) r- (optionally substituted aryl), where r is an integer M, _C (0) 0- (optionally substituted aryl) or -C (0) N (H)-(optionally substituted aryl). In another specific embodiment, R3 is -C ( 〇H optionally substituted aryl), where the substituent, when present, is fluorenyl, pseudohalo, alkyl, alkoxy, alkanedioxy, haloalkyl, nitro, cyano , -C (0) 0-alkyl, aryl, or -SO2F. In another embodiment, R3 is -C (o) -heteroaryl. In another embodiment, 'R3 Is -C (O) -alkyl. In another embodiment, R3 is hydrogen. In another embodiment, R3 is -S02- (optionally substituted aryl), wherein the substituent is 'When present' is an alkyl, commercial, alkoxy or haloalkoxy group. In another specific embodiment, R3 is -C (〇) _ (CH2) r_aryl, where I * Is 1 or 2. In another specific embodiment, r3 is _c (〇 > 〇_ (optionally substituted taryl), wherein the substituent, when present, is self-radical, alkoxy Or alkyl. In another specific embodiment, R3 is -c (〇) N (HM optionally substituted aryl), wherein the substituent, when present Is a fluorenyl group, an alkoxy group, or an alkyl group. In another specific embodiment, R3 is selected from the group consisting of hydrogen, hepta (〇) _shichlorophenyl), 85585 -48- 200307684 C (0)- (4 · fluorophenyl), -C (0)-(2-creanyl), -C (〇H2 + dichlorophenyl), -C (0)-(3-nitrophenyl), -C (〇Hphenyl), -C (O) · (methyl), -C (0) _ (4-third-butylphenyl), -S02- (4-methylphenyl), -S02 -(4 · Third-butylphenyl), -C (〇H2-methoxyphenyl), -C (0)-(3-methoxyphenyl), _C (0)-(4-methoxy Phenyl), -C (O)-(benzyl), -C (0) 0_phenyl, -C (0) 0- (4 · chlorophenyl), _C (0) 0- (4 · methyl (Oxyphenyl), -C (0) 0- (4-methylphenyl), -C (0) N (H) -phenyl, -C (0) N (H)-(4-chlorophenyl ), -C (0) N (H)-(2,4-dichlorophenyl), -C (0) N (HM4-methoxyphenyl), -C (0) N (H)-(4 -Methylphenyl), -C (0)-(3,4-methylenedioxyphenyl), -C (O) -n-octyl, C (0) _CH2CH2 phenyl, _S02- (4-chlorophenyl), -S (V (4-methoxyphenyl), 402- (3,4-dimethoxyphenyl), _802_ (4-trifluoromethoxyphenyl),-(:( 0)-(2,3 · difluorophenyl), -C (0)-(2,4-difluorophenyl), -C (0)-(2,5-di Phenyl), -C (0)-(2,6-difluorophenyl), -C (0)-(3,4-difluorophenyl), -C (〇H3,5-difluorophenyl) ), -C (0)-(2,3,4-trifluorophenyl), -C (〇H2,3,6-trifluorophenyl), -C (0)-(2,4,5- Trifluorophenyl), -C (0) _ (2,3,4,5-tetrafluorophenyl),-(:( 0)-(2,3,4,5,6-pentafluorophenyl) , -C (〇H2,5-bis (trifluoromethyl) phenyl), -C (0)-(3,5-bis (trifluoromethyl) phenyl), -C (0)-(2- Trifluoromethylphenyl), < (0)-(3-trifluoromethylphenyl), -C (0)-(4-φtrifluoromethylphenyl), -C (0)-( 2-fluorophenyl) '<: (0)-(3-fluorophenyl), -C (0)-(4-nitrophenyl), -C (0)-(3-nitro- 4-methylphenyl), -C (0)-(4-methoxycarbonylphenyl), -C (0)-(3-pyridyl), -C (0)-(4-eridinyl) , -C (0)-(3-cyanophenyl), -C (0)-(3,4-dimethoxyphenyl), -C (〇H2-methylphenyl), -C ( 0)-(4-methylphenyl), -C (0)-(2-chlorophenyl), -C⑼- (2-fluorenyl), _C (0)-(4-biphenyl),- C (0 > (4-fluorosulfofluorenylphenyl), -c (0 > (3-methylphenyl), and -C (0)-(3-chlorophenyl). In another specific embodiment, R4 is hydrogen, optionally substituted alkyl, 85585 -49- 200307684 optionally substituted alkenyl, optionally substituted alkynyl, -c (0) 〇r2G or -C (0) N (R21) R22; where R20, R21 and R22 are each independently hydrogen, optionally substituted alkyl, optionally substituted fluorenyl, optionally substituted alkynyl, optionally substituted Cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, or optionally substituted heteroaralkyl. In another specific embodiment, R4 is hydrogen, optionally substituted alkyl, _C (0) 0H, -C (0) 0-alkyl, or -C (0) N (R21) R2 2; wherein R21 and R2 2 are each independently hydrogen, optionally substituted alkyl, or together with the nitrogen atom to which they are attached to form a optionally substituted heterocyclic or heteroaryl ring. In another embodiment, R4 is hydrogen, optionally substituted alkyl, -C (0) 0H, -C (0) -0-alkyl, or -C (0) N (R21) R2 2 ; Wherein R21 and R2 2 are each independently hydrogen or alkyl, or together with the nitrogen atom to which they are attached to form a heterocyclic ring;

In another specific embodiment, R4 is hydrogen, methyl, ethyl, _C (〇) 〇H, -C⑼〇CH2CH3, -c (0) -n (h) ch2ch3, -c (o). Hydropyridyl or -CH2OC (0)-(4-denyl). In another embodiment, R5, R6 and R7 are each independently hydrogen or optionally substituted alkyl. In another embodiment, R5, R6, and R7 are each independently hydrogen or alkyl. In another embodiment, R5, R6 and R7 are each hydrogen. In another specific embodiment, R5 is hydrogen, and 圮 and 7 are each replaced by: ^ group. In another embodiment, R5 is hydrogen, and R6 and R7 are each optionally substituted lower alkyl. In another specific embodiment, R8 is optionally substituted alkyl, halo, pseudohalo, -C (〇) OR23 or _〇r27; wherein R23 is optionally substituted 85585 -50- 200307684 and R2 7 is optionally substituted alkyl. In another specific embodiment, R8 is an alkyl group, a halo group, -C (0) OR23 or -OR27; wherein r23 is an alkyl group; and R2 7 is an antigroup. In another embodiment, r8 is hydrogen, methoxy, chloro, iodo, fluoro, methyl or -C (0) 0-ethyl. In another embodiment, n is 0, 1, or 2. In another specific embodiment, R9 is hydrogen or alkyl. In another specific embodiment, R9 is 氲. In another specific embodiment, the compounds provided in the compositions and methods provided herein are of formula ①N-hexindole, wherein R1-R9 is selected as described above. In another specific embodiment, the compounds used in the compositions and methods provided herein are pyridoxindoles of formula (11), wherein R1 to R9 are selected as described above. 2. The preferred compounds of this specific embodiment are the following compounds, wherein: η is 0 or 1; A is -N (R9)-; R1 is optionally substituted aryl or _C (0) 0R14; R2 Is hydrogen or optionally substituted alkyl; R3 is hydrogen, _C (〇) R10 or -S (〇) 2R10; R4 is hydrogen, optionally substituted alkyl or ((〇) 〇R2〇; RRR And r9 are each independently hydrogen or optionally substituted tiger radical; R8 is hydrogen or -QR2 7; each R10 is independently a substituted alkyl group, optionally substituted aryl group, or optionally substituted aromatic group Alkyl group; 85585 200307684 R14 is optionally substituted slope group; and R is optionally substituted slope group. In the specific embodiment, the compound used for the group of people's toiletry formula is ① Nitrogen indole, compound of formula hydrazone

Wherein W-R9 is selected as described above for the compound of formula (I) or formula (π). In this specific embodiment, the preferred embodiments are the following compounds, wherein: η is 0 or 1; A is _N (R9)-; R1 is _C (0) 0Ri4; R2 is hydrogen; R3 is Optionally substituted alkyl, optionally substituted aryl, optionally substituted aralkyl, or optionally substituted heteroaralkyl; R4 is hydrogen, -C (0) R18, -C (〇) 〇R20 or -C (0) N (R21) (R22); R5, R6 and R7 are each independently hydrogen or optionally substituted alkyl; R8 is optionally substituted alkyl, optionally substituted aromatic OR9; OR27; R9 is hydrogen or optionally substituted alkyl; R14 is hydrogen or optionally substituted alkyl · 85585 -52- 200307684

Rl8 is optionally substituted heterocyclic group; optionally substituted alkyl; R /, R each independently represents an optionally substituted alkyl group, or R21 and R22 and theirs are connected together to form a nitrogen atom Optionally substituted heterocyclyl ring; and R27 is optionally substituted alkyl, optionally substituted fluorenyl, optionally substituted decyl, or optionally substituted aryl. In this preferred embodiment, the preferred compound is selected from the following: U-dimethyl-1,2,3,6-tetrahydronitrogeno [4,5 heptanecarboxylic acid ethyl ester ; And 1,1,3,6-tetramethyl-l, 2,3,6-tetrahydronitrogen is eh [4,5-bH indole-5-carboxylic acid ethyl ester. In this specific embodiment, another preferred embodiment is the following compound, wherein: η is 0 or 1; A is Carved 9) _; R1 is -C (0) 0R14; R2 is hydrogen; R3 is- (3 (0) 111 G; R4 is hydrogen or -C (0) OR20; R5, R6, and R7 are each hydrogen; R8 is optionally substituted alkynyl, optionally substituted aryl, functional group, or -OR2 ?; R9 is hydrogen; R10 is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted cycloalkyl, optionally substituted aromatic group, optionally substituted heterocyclic Cyclic group, optionally substituted heteroaryl group or optionally substituted hetero 85585 -53- 200307684 aryl group, R14 is optionally substituted alkyl group, optionally substituted alkenyl group, and moon phase Substituted alkynyl or optionally substituted arsenyl; r20 is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, or optionally substituted aralkyl And R27 is optionally substituted alkyl, optionally substituted fluorenyl, optionally substituted decyl, or optionally substituted aromatic radical. In this specific embodiment, A preferred embodiment is the following θ, where: η is 0 or 1; A is -N (R9) _; R1 is-(XO) OR14; R2 is hydrogen; R3 is-. (0 0; R4 is hydrogen, optionally substituted alkyl, optionally substituted aryl, or `` c (o) or2〇; R5, R6, and R7 are each independently hydrogen or optionally substituted alkyl; R8 is Optionally substituted alkyl, _ or -OR27; R9 is hydrogen; R10 is optionally substituted aryl; R14 is optionally substituted alkyl, optionally substituted feminine, optionally substituted The alkynyl 1 group or optionally substituted paroxy group 'R20 is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, or optionally substituted aralkyl; And 85585 -54- 200307684 R27 are optionally substituted alkyl groups. In this preferred embodiment, the preferred compound is a compound selected from the group consisting of 3- (4-p-methoxybenzyl) -1-Methyl-1,2,3,6-tetrahydronitrogeno [4,5-b] ^ indole-5-carboxylic acid ethyl ester; 3-Sunflower fluorenyl-μmethyl-1,2, 3,6-tetrahydronitropyrene [4,5Hepta] indole-5_carboxylic acid ethyl ester; 3- (4-p-methoxybenzoyl Group) -1,1-dimethyl-1,2,3,6-tetrahydronitrogen is eh [4,5 hept] indole-5-carboxylic acid ethyl ester; and 1,1 · dimethyl-3 -Sunflower fluorenyl · 1,2,3,6-tetrahydrazine benzo [4,5 hepta] indole · 5 · carboxylic acid ethyl ester. In this specific embodiment, another preferred embodiment is The following compounds, wherein: η is 0 or 1; A is -N (R9)-; R1 is optionally substituted heterocyclic group, ((OPR14, ((SPR14, -CXC ^ SR14, -CCCONCR15) Ri6,- qCON ^ NR16 or 5) 1116; R2 is hydrogen; R3 is -cccor1 0; R4 is hydrogen, optionally substituted alkyl, -C (0) R18, -C (0) 0R2G, or -C (0) N (R2 ”r2 2; R5, R6 and R7 are each independently hydrogen, optionally substituted alkyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, _〇R14; -S ( 0) 2R14, -N (R15) R16, _C (〇) r18, -C⑼〇R2 0 or seven (〇) N (R2 1) R2 2; 85585 -55- 200307684 or R6 and R7 and their connected Carbon together forms a heterocyclic group optionally substituted or keto group together, and R5 is as described above; R8 is optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, Halo, -C (0) 0R23, -OR27 or _N (R28) R29; R9 is hydrogen or optionally substituted alkyl; R10 is phenyl, substituted by one or more Q1 groups selected from: halo, pseudo Halo, haloalkyl or poly || alkyl; R14, R15, R16 and R17 are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted cycloalkyl , Optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; or R15 together with R16 and the nitrogen atom to which they are attached Optionally substituted heterocyclyl ring, and R14 and R17 are as described above; or R18 is optionally substituted alkyl; R2 0, R2 1 and R2 2 are each independently hydrogen or optionally substituted healthy group 'R2 3 is an optionally substituted alkyl group; R27, R28, and R29 are each independently hydrogen, optionally substituted amidyl, substituted aralkyl group, -C (〇) R3G, -C (0) 0R31 or _C (〇) N (R32) R33; R30 is optionally substituted aryl or optionally substituted heterocyclic group; R31 is optionally substituted alkyl, optionally substituted Aryl or Optionally substituted aralkyl; and R32 and R33 are each independently hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted arylfluorenyl , Optionally substituted heterocyclic groups, optionally substituted heteroaryl groups, or optionally substituted 85aryl-56- 200307684 optionally substituted heteroaryl groups; or R together with R and the nitrogen to which they are attached form a A substituted heterocyclic ring or optionally a substituted heteroaryl ring. The preferred compounds of this preferred embodiment are the following compounds, selected from the group consisting of the following: 3- (3,4-difluorobenzylidenemethyl · tetrahydronitropyre [4,5_b] oxin_5_ Ethyl carboxylate; 3- (3,4-difluorobenzylidene dimethyl 4,2,3,6-tetrahydronitrocarba [4,5_b ^ 丨 Homo-5-carboxylic acid ethyl ester; 3 -(3,4-monofluorobenzylmethyl) -1,1_dimethyl_l, 2,3,6-tetrahydronitrocarba [4,5-b] p? 丨 -5-carboxy Isopropyl ester; 3- (3,4-difluorobenzylidene) -i-methyl ^^, cardiac tetrahydronitrogen is entrained [4,5 heptadol | isopropyl acetic acid; Μ3Λdifluoro Benzamidine) -2 • methyl_1,2,3,6-tetrahydronitrocarba [4,5hepta] indole-5- cynylbutylamine; 3- (3,4-di Fluorobenzyl) -1-methyl_; ι, 2,3,6 · tetrahydronitropyro [4,5-b] radol-5-carboxylic acid cyclobutylphosphonium amine; cyclobutyl 3 -(3,4-difluorobenzylidene) -1,1-dimethyl · 1,2,3,6 · tetrahydronitrogeno [4,5-b] indole-5-carboxamide ; 3- (4-chlorobenzylidene) -1-methyl-1,2,3,6-tetrahydronitrogeno [4,54)] oxindole-5-carboxylic acid ethyl ester; 3- (4-Aminobenzylidene) -1,1 · dimethyl-1,2,3,6-tetrahydronitrocarba [4,5 七] # 丨 indole-5-carboxylic acid ethyl ester; Η Benzylmethylamino -3- (3,4-difluorobenzylidene) -1,1_dimethyl-1,2,3,6-tetrahydro 85585 -57- 200307684 nitrogen is benzo [4,5 hepta] oxindole Ethyl-5-carboxylic acid; 3- (4-fluorobenzyl) small methyl-1,2,3,6-tetrahydronitrogeno [4,5hepta] oxindole-5-carboxylic acid ethyl Ester; 3- (4-fluorobenzyl) -2-methyl-1,2,3,6-tetrahydronitrogeno [4,5H >? indole-5-carboxylic acid n-propane Esters; and 3- (4 • fluorobenzylidene) -2-methyl-1,2,3,6-tetrahydroazepine [4,5-b] indole-5-carboxylic acid cyclobutyl Lamine. In this preferred embodiment, another group of preferred compounds is selected from the group consisting of 8-dibenzylamino-3- (4 · fluorobenzyl) -φ U · dimethyl · 1,2,3,6-Tetrahydronitrogen benzo [4,5 hepta] indole-5-carboxylic acid ethyl ester; 8-[(2-chloroethyl) methylamino] -3- (4_ Fluorobenzyl) -1,1-dimethyl-1,2,3,6-tetrahydronitrogeno [4,5 hepta] oxindole-5-carboxylic acid ethyl ester; 8- (3,3 -Dimethylureido) -3- (4-fluorobenzylidene) -1,1-dimethyl-1,2,3,6-tetraargonium hydride [4,5-b: N indole -5_ carboxylic acid ethyl ester; 3- (4-Gabenzoate) -1,1-dimethyl-8- [methyl (tetrazolium p each-4-hexyl) amino] -1, 2,3,6-Tetrahydronitrogeno [4,5Hepta] Ethylindole-5_carboxylic acid ethyl ester; benzyl) -1,1-dimethyl-8- (trimethyllunyl group ) 1,2,3,6-tetraazalactone ethyl [4,5-b] indole-5-carboxylic acid ethyl ester; 3- (4- ^ benzyl) -1,1-dimethylformate Ethyl-8- [methyl (morpholin plin-4-yl) amino] -1,2,3,6-tetrahydronitrogeno [4,5hepta] oxindole-5-carboxylic acid ethyl ester ; 3- (4-fluorobenzylidene) · 1,1-dimethyl (hexahydropyridine small carbonyloxy) -1,2,3,6-tetrahydronitrogen [4,5 七] Ethyl-5-carboxylic acid ethyl ester; 3- ( 4-Gasbenzyl dimethyl-8- (4-methyl 7T mouse b-hu-1-ylamine methyloloxy) -1,2,3,6-tetrahydronitrogen [4 , 5-bH 丨 Indole-5-carboxylic acid ethyl ester; 3- (4-fluorobenzylfluorenyl) -1,1-dimethyl-8-phenethylaminemethylfluorenyloxy-1,2, 3,6-tetra85585 -58- 200307684 Hydrogen-nitrogeno [4,5-b] indole-5_carboxylic acid ethyl ester; 3- (4-fluorobenzyl) -1,1-dimethyl -8Heptaphen-2-ylmethylaminomethylamidooxy) -1,2,3,6-tetrahydronitrogeno [4,5hepta] oxindole-5-carboxylic acid ethyl ester; 3- (4-Fluorobenzyl) -1,1-dimethyl-8- (crean-2-ylmethylaminemethylammonyloxy) -1,2,3,6-tetrahydronitrogen [4,5Hepta] Indole-5-ethyl acetic acid; 8- (4- ^ benzylidenemethylamino) -3- (4-fluorobenzyl) -1,1-dimethyl -1,2,3,6_ Tetrahydronitrogero [4,5 七] 4 丨 Homo-5-acrylic acid ethyl ester; 8- (3-cyclopropyl small methylureido) -3- (4- Fluorobenzyl) · 1,1-dimethyl-1,2,3,6_ Tetrahydronitrogeno [4,5-b] oxindole-5-carboxylic acid ethyl ester; 3- (4-Ga Benzethenyl) -1,1-dimethyl-8- (1-methyl-3 · ρ than dian-2-ylmethylcarboxyl) _1,2,3,6-tetrahydronitrogen [4,5-b] Ethyl-5-butyric acid ethyl ester; 8 · cyclobutylamine formamidine Oxy-3--3- (4-fluorobenzylidene) _1,1_dimethyl-1,2,3,6-tetrahydronitrocarba [4,5-bH 丨 indole-5-carboxylic acid ethyl ester ; 8-Cyclopentylamine formamyloxy-3- (4-fluorobenzylidene) -1,1-dimethyl-1,2,3,6-tetrahydronitropyrene [4,5 -b] ethyl indoxy-5-metanoate; 8-cyclohexylamine formamyloxy-3- (4-fluorobenzylidene) -1,1-dimethyl-1,2,3, 6-tetrahydronitropyridine [4,5-b] indoma-5-acrylic acid ethyl ester; 3- (4-fluorobenzylidene) -1,1-dimethyl-8- (5-methyl Pyridoxin-2-ylmethyl [amine formamyloxy] -1,2,3,6-tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid ethyl ester; 3. · (4 · Acetobenzyl) -1,1-dimethyl-8-methylcarbamic acid, lactyl-1,2,3,6-tetraazanitrogen, [4,5-b] indole Ethyl-5-carboxylic acid; 3- (4-fluorobenzylidene) -1,1-dimethyl isopropylamine formamyloxy · 1,2,3,6-tetrahydroazepine Ethyl [4,5-b] oxindole-5-carboxylic acid ethyl ester; 8-(-azatetrafluoren-1-carbonyloxy) -3_ (4-fluorobenzyl) -1,1-dimethyl 1,2,3,6- 85585 -59- 200307684 Tetrahydronitrogeno [4,5_b] W 丨 Indole-5-carboxylic acid ethyl ester; M4-fluorobenzyl) -1,1-di Methyl each (Oxy) -1,2,3,6-tetrahydroazepine [4,5-b] indole-5-carboxylic acid ethyl ester; 8-cyclopropylamine formamyloxy-3- (4 -Fluorobenzyl) -1,1-dimethyl ^ 2,3,6-tetrahydronitrogeno [4,5hepta] oxindole-5-carboxylic acid ethyl ester; 8- (ethyl (isopropyl Group) carbamoyloxy) -3- (4-fluorobenzylidene) -1,1_dimethyl_1,2,3,6-tetrahydronitrogeno [4,5hepta] indene Ethyl indole-5-carboxylic acid; 3- (4-fluorobenzyl) -1,1-dimethyl each (pyridin-2-ylmethylamine formamyloxy) · 1, 2, 3 , 6-Tetrahydronitrogeno [4,5-bH 丨 indol-5-carboxylic acid ethyl ester; 3- (3,4 · difluorobenzyl) -1-, 1,6-trimethyl-1, 2,3,6-Tetrahydronitropyrene [4,5Hepta] indole-5-carboxylic acid ethyl ester; 3- (4 • fluorobenzyl) -1,1-dimethyl each -3-ylmethylamine formamyloxy) -1,2,3,6-tetrahydronitrogen entrains [4,5-bH 丨 Homo-5 · carboxylic acid ethyl ester; 8-ethane Ethyl-3- (4-aminobenzyl) -1,1-dimethyl-1,2,3,6_tetraazazepine and [4,5-b; H] indole carboxylic acid ethyl ester ; 3- (4-Fluorobenzyl) -1,1-dimethyl-8- (tetrahydropyrrole-1-carbonyloxy) -1,2,3,6 · Tetrahydronitrogen [4 , 5-b] indole-5-carboxylic acid ethyl ester; 8-diethyl Carboxamidooxy-3- (4-fluorobenzylidene) -1,1-dimethyl-1,2,3,6-tetrahydronitrogeno [4,5hepta] pyridin-5 -Ethyl hexanoate; 8-dimethylamine formamyloxy-3- (4-fluorobenzylidene) -1,1-dimethyl-1,2,3,6-tetrahydroazepine Benzo [4,5-b] indolecarboxylic acid ethyl ester; 3- (4-fluorobenzylfluorenylhydrazone, 1-dimethyl each (morpholine-4-carbonyloxy) -1, 2, 3 , 6 · Tetrahydronitrogero [4,5Hepta] indole-5_carboxylic acid ethyl ester; 8-diisopropylamine formamyloxy-3- (4-fluorobenzyl) -1 1,1-dimethyl-1,2,3,6- 85585 -60 200307684 Tetrahydronitrogeno [4,5-bH 丨 indole-5-carboxylic acid ethyl ester; 3- (4-fluorobenzidine ) -1,1-dimethyl-8- (4-methyl-hexahydropyridine small carbonyloxy) -1,2,3,6-tetrahydronitrogeno [4,5Hepta] pyridine Ethyl-5-carboxylic acid; 3- (4-fluorobenzylidene) -1,1-dimethyl-8- (2-ketoimidazolinidine small carbonyloxy > 1, 2, 3, 6-tetrahydronitropyrene [4,5-b] indole-5_carboxylic acid ethyl ester; 3- (4-fluorobenzylidene) -1,1-dimethyl each (methyl-phenyl -Aminomethylamidoyl) -1,2,3,6-tetrahydronitrocarba [4,5-b] indole-5-carboxylic acid ethyl ester; 8- (2-dimethylaminoethyl) Carboxamidooxy) -3- (4-fluorobenzyl ) _1,1_dimethyl-1,2,3,6-tetrahydronitrocarbazone [4,5-b] indole-5-carboxylic acid ethyl ester; 3- (4-fluorobenzylfluorenyl) Dimethyl (2-pyridyl-ethylaminomethylamidooxy) -1,2,3,6-tetrahydronitrogeno [4,5_b] ^ indole-5-carboxylic acid ethyl ester; 3- (4-fluorobenzylhydrazine H, l-dimethylhexyl (pyridin-4-yl-methylaminomethylammonyloxy) -1,2,3,6-tetrahydronitrogeno [4,5 -b] indium-5-acetic acid ethyl ester; 3- (4-fluorobenzyl) _u_dimethyl each phenoxycarbonyloxy group ·, 2,3, tetrahydronitrile 117 [4,5_b] p? 丨 Ham-5_acetic acid ethyl ester; 8-fluorenyloxy-3- (4-fluorobenzyldimethyldimethyl H3 mediates tetrahydronitrogen [4,5_b ] Indole-5-carboxylic acid ethyl ester; and 8- (2-monomethylaminoethoxycarbonyloxyfluorobenzylhydrazone) · dimethyl-1,2,3,6-tetrahydronitrogen And [4,5_b; N indole ethyl carboxylate. In this embodiment, another preferred embodiment is the following compound, wherein: η is 0 or 1; A is -N (R9) 4 R1 is -C (0) 0RW; 85585 200307684 R2 Is hydrogen; r3 * -c (o) r1 (); R4 is hydrogen, optionally substituted alkyl or -C (〇) Rl 8; R5, R6, and R7 are independently rats or depending on the condition Substituted alkyl; R8 is optionally substituted alkyl, halo or " "〇R27; R9 is hydrogen; R10 is optionally substituted heterocyclyl or optionally substituted heteroaryl; R18 Is optionally substituted alkyl; and R2 7 is optionally substituted. In this specific embodiment, another preferred embodiment is the following compound, wherein: η is 0 or 1; A is -N (R9)-; R1 is -C (0) 〇Ri4; R2 is hydrogen; R3 is -qcONCR11)! ^ 0; R4, R5, R6, r7 and R9 are each hydrogen; R8 is optionally substituted alkyl, ii or -OR27; R1G is optionally substituted aryl; R11 is Hydrogen; R14 is optionally substituted alkyl; and R27 is optionally substituted alkyl. In this specific embodiment, another preferred embodiment is the following compound 85585 -62- 200307684 η is 0; A is -N (R9) _; R1 is -C (0) 0R14; R2 is hydrogen ; R3 is -C (0) N (Ru) R1 (); R4, R5, R6, R7, and R9 are each hydrogen; R10 is optionally substituted alkyl, optionally substituted aryl, and optionally Substituted aralkyl, optionally substituted heterocyclyl, or optionally substituted heteroaryl; R11 is hydrogen or optionally substituted alkyl, and R14 is optionally substituted alkyl. In this specific embodiment, another preferred embodiment is the following compound, wherein: η is 0 or 1; A is -N (R9)-; R1 is -C (0) 0R14; R2 is hydrogen; R3 is -C (0) OR10; R4, R5, R6, R7, and R9 are each nitrogen halide or -OR2 7, and R8 is optionally substituted alkyl, alkyl, optionally substituted aryl, or As appropriate, R10 is optionally substituted aralkyl; R11 is hydrogen or, as appropriate, f U 'R14 is optionally substituted, and 85585 -63- 200307684 R27 is optionally substituted Maung Kee. In this specific embodiment, another preferred embodiment is the following compound, wherein: η is 0 or 1; A is -N (R9)-; R1 is -C (0) OR14; R2 is hydrogen; R3 -S (0) 2R10; R4, R5, R6, R7 and R9 are each hydrogen; _R8 is -OR27;

Ri 〇 is optionally substituted square or optionally substituted heteroaryl; R11 is hydrogen or optionally substituted alkyl; R14 is optionally substituted alkyl; and R27 is optionally substituted alkyl. In another specific embodiment, the compounds provided in the compositions and methods provided herein are compounds of the formula (I) nitrohexindole (wherein the compound is formula Yang). Compounds: 85585 r \; r6 r5

Wherein R1 to R9 are as defined in the above summary of the compound of formula ①. In this specific embodiment, the preferred embodiment is the following compound, whose -64- 200307684 η is 0; R is _N (R9) _; R1 is ((0) 01114 or -CXC ^ NCR15) 1116; R2 is hydrogen; R3 is optionally substituted aryl, -C (0) R1G; -C (0) 0R1G; or C (0) N (Ru) Ri〇; each of R4, R5, R6, R7, and R9 For hydrogen

R1G is optionally substituted aryl or optionally substituted aralkyl; R11 is hydrogen; R14 is optionally substituted alkyl; R15 is hydrogen; and

R16 is optionally substituted alkyl or optionally substituted aralkyl. I. Preparation of Compounds of the Invention The starting materials in the synthesis examples provided herein are either available from commercial sources or via literature procedures. All commercially available compounds are

It is used under further purification unless otherwise indicated. CDCl3 (99 8% D, Cambridge Isotope Lab) was used in all experiments as shown. The proton (1 homonuclear magnetic resonance (NMR) optical system was recorded on a Bmker Av sister 400 MHz Nmr spectrometer

. The significant absorption peaks are listed in the table, and typically include: proton number and multiple ohms (single peak, d, double_; t, triplet; mouth, quadruple; ㈤, multiplet, broad). Chemical shifts are reported as "parts per hundred" relative to tetramethylpyrene. Low resolution mass spectrometry (ms) was obtained as electrospray ionization (ESI) shells, which were recorded on sc] [EX HPLC / MS instrument using reverse phase conditions (acetonitrile / water, 0.05% trifluoroacetic acid) 85585 -65- 200307684. Flash chromatography was performed using Merck Silicone 60 (230-400 mesh) in accordance with the proposed standard (Still et al. (1978) J. Org. CT ^ m · 43: 2923). It should be understood that in the description below, combinations of substituents and / or variables of the chemical formulae depicted are allowed only if such combinations result in stable compounds. Those skilled in the art should also understand that in the methods described below, the functional group of the intermediate compound may have to be protected by a suitable protecting group. Such functional groups include hydroxy, amine, thio and carboxylic acids. Suitable protecting groups for hydroxyl groups include trialkylsilyl or diarylalkylsilyl (e.g., tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or trimethylsilyl) , Tetrahydropiperanyl, fluorenyl and the like. Suitable protecting groups for amine, formamidine and guanidino include tert-butoxycarbonyl, benzyloxycarbonyl and the like. Suitable protecting groups for mercapto include -C (0) -R (where R is alkyl, aryl or aralkyl), p-methoxyfluorenyl, trityl and the like. Suitable protecting groups for carboxylic acids include alkyl, aryl or aralkyl esters. Protecting groups can be added or removed according to standard techniques known to those skilled in the art and as described herein. The use of protecting groups is described in detail in Green, T.W., and RG.M. Wutz, only to be synthesized. J: The Protected Shame (1991), 2nd edition, Wiley Interscience. The protective group may also be a polymer resin such as Wang resin or 2-chlorotriphenylmethane chloride resin. Generally speaking, the starting ingredients can be obtained from sources such as Aldrich, or synthesized from sources known to those skilled in the art (see, for example, Smith and Mm ^ March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structures,% 5 edition (Wiley Interscience, New York)). Furthermore, the R group is selected from the ingredients as indicated in the specification of this patent 85585-66-200307684, and can be connected to the starting ingredients, intermediate ingredients, and / according to synthetic systems known to those skilled in the art. Or the final product. In the following figures, unless otherwise indicated, various R groups are as defined above in the Summary of the Invention. For the reaction conditions of each scheme, the skilled person can easily determine which option is feasible for each R group. As depicted in Scheme 1 below, n-propyl 3-bromopyruvate and isopropyl ester (3) are made by the halogenation of the corresponding alcohols with 3-bromoacetonium chloride ( Teague et al., CAem 1995, 5, 2341-2346). Scheme 1 〇βγ \ Α, 1

Me〇CHCl2

C〇2H 〇 Br, ^ c〇ci 2

R〇H 〇 Today Br, ^ C〇2R 3 As depicted in Figure 2 below, some substituted tryptamines are not commercially available, and are made from indigo, which can be prepared by Fischer indole synthesis Cheng (Smith & March, Marc / z Wu Gao Zhengyi Man Yunxue, 5th Edition, John Wiley & Sons: NY, 2001, pp. 1453-24). Mesitylation of indole 3 to formyl aldehydes 4 (Mor et al. MM C% 1998 1998 4 / 3831-3844). The 3-methylamidoindole 4 and 1 · nitroalkane are reacted in the presence of ammonium acetate at a high temperature to obtain a nitro compound 5, which is reduced by catalytic hydrogenation or lithium aluminum hydride, and treated with HC1. Thereafter, tryptamine hydrochloride 6 was obtained. 85585 -67- 200307684 Scheme 2

p〇Cl3, DMF 1) HrPd / C or LiAIH4

i 1.nitroalkane BnNH2, PhMe, reflux 5 Η 6

2) HCI € 〇

Ah r4 NHo HCI

H As described in Scheme 3 below, tryptamine can also be substituted by alkylation and made from the reduction of 3〃? Indolacetonitrile. Gramine 7 is commercially available, or is synthesized from commercially available substances through reactions such as nitration at the 6-position, or synthesized from indole 4 (Bκ) λνη and Carrison, CAE · H955, 77, 3839-3842). It was treated with decomposed formazan to form a quaternary salt, which was replaced with cyanide to obtain 3-pyridylacetonitrile 9. The Boc group was used for solid protection of 9, followed by alkylation and removal of protection, to obtain 10.10 with the reduction of lithium aluminum hydride, followed by treatment with hydrochloric acid to obtain tryptamine hydrochloride 7. When benzyl is used as the nitrogen protecting group of 9, it is removed after the reduction of the nitrile group. The benzofuran groups and the benzophenanthrene group are all derived from the corresponding acetonitrile 10 via reduction with lithium aluminum hydride. 85585 68- 200307684 Schema 3 R8

Η 4

CH20, NHMe2 AcOH

1) LiALH4 X = NH, 0, S 2) HCI

R

1) (Boc) 2〇 1) BnB "/ Na〇H, catalyst 2) Br2 (CH2) n + 2 /

1) LiALH4 2) Na / NH3 (〇 3) HCI

As depicted in Scheme 4 below, the substituted tryptamine 7 can be condensed with aldehyde via 3-pyridylacetonitrile 9 in the presence of a test compound, and then reduced to obtain compound η, which is reduced to obtain tryptamine 7 While made. Scheme 4 R8to

, CN R6CH〇, alkali

CN 1) Raney-Ni, NH2NH2 R6

Boc 1 2) HC 丨 11

As depicted in Figure 5 below, the formation of a nitrogen ring can be achieved by a pictet_Spengler reaction, followed by rearrangement. Nitrogen derivatives provide alkylation or acidification to provide the final product (14). Put tryptamine, benzopyran-3-ylamine and benzo [b] thiophen-3-ylamine 7 or its hydrochloride, and 3-dentylpyruvate 3 in their corresponding alcohols (when used In free state base, enter with HCi. 85585 -69- 1 Base / RX (R = H, R6, R7) 2

In TFA 200307684, the hexahydropyridine derivative 12 is obtained by treatment under reflux, and then it is heated in the presence of TEA or in pyridine to obtain a nitrogen-apocrine compound 13. Further treatment with fluorenyl or% fluorenyl chloride, isocyanate, and chloroformate in the presence of TE A13 provided the final product 14 (Kuehne et al. (1985) ^ M 50: 919-924). Scheme 5

7

, ΝΗ C〇2R

14 pyridine reflux

α V R8rrV ^ _R5 r3cicis3, r 13 • '^ nh 0 s 2-The derivative of 2-nitropyridine is described in the following scheme' ', the 2-ethoxycarbonyl-substituted compound 15 is hydrolyzed, and The acid 16 is obtained, and the gas is converted into amine 17. 17. The tritiated effect of 17 in the presence of TEA, and the obtained person produces the amine group product 18.

〇

ArCOCI / NEt3 f | 1R22rn

18 17 85585 -70- 200307684 As described in Scheme 7, the 5-ester group is hydrolyzed to obtain the 5-edge acid 2i. Hydrolysis of the ubiquitin 19 group yields extremely low yields. Therefore, the compound was converted into the compound 20 protected with (Uth oxycarbonyl) group, which was hydrolyzed under standard alkaline hydrolysis conditions to obtain acid 21, and the boc group was also removed. Round 7

NaOH Me0H-H20 α

1 νη co2h 21 As depicted in Scheme 8 below, hexahydroindole nitrogen can be synthesized by reduction followed by tritiation. The double bond in compound 22 is returned to Na'BH3CN to obtain a saturated brew 23, which is then basified in the presence of τΕΑ to obtain 24.

Round 8

... as described below, the rider in Formula 9, 5_Laike can be processed by ^ step reaction sequence, h from 5th day & compound 22 is treated with amines, and the corresponding acid amines, in the presence of TEA, It is converted to 26 by tritiation. 26 The compound is obtained by the oxidation of the third-butyl hypochlorite. "85585 -71- 200307684 Scheme 9

r3ci 'νεϊΓ

After the chemical reaction, the cleavage is performed to obtain the acid 29. 29 after coupling with CDI (alcohols, amines, amines, thiols), followed by the oxidation of the third-butyric acid with hypochlorite To place a double bond and get 31. Formula 10

The more general technique of Scheme 9 is described in Scheme 下文 below. Diamine

As depicted in Scheme n below, compound 32 can be derived by donkeying. Compound 32 is fluorinated in the presence of TEA to a monofluorinated product 33 and a difluorinated product 34. 85585 -72- 200307684 Scheme 11

°° 34 As depicted in Figure 12 below, is it possible? A substituent at the 6N_ position. Compound 35 is treated with a base and an alkyl autogenate at the indol nitrogen to obtain compound 36 by alkylation. Round 12

As depicted in Scheme 13 below, 'compound 22 was treated with 1 ^^% 〇11 reagent (Curphey et al., 2002, 67, 6461-6473) in toluene, and It is then treated to obtain thionyl group 37, which is then halogenated with 4-fluorobenzyl chloride to obtain compound 38. Scheme 13

R3C1 NEt3

Scheme 14 depicts the introduction of 3-alkyl / aryl. Compound 22 was treated with NaH and then with RX to introduce an alkyl group into the 3-position to obtain compound 39, 85585 -73- 200307684, which is a mono-fluorinated product 40 in two hours; The aromatic group is introduced through a coupling of 22 and a rogyl boron: k (Lam et al., Chi You Heng 2 delete, 仏 34i5_3418) ′ after introducing the double bond by oxidation, to obtain the product 42. Scheme 14

As depicted in Figure 15 below, the heterocyclyl can be introduced from the acid fen at the 5 • position. For example, oxazoline is made from individual amine alcohols and saturated acid hydrazones by forming amines 43. Next, in Shancai, thalliumamine 43 was subjected to cyclization through successive treatment with thionyl dichloride, then 6NNaOH, and catalytic PTC to obtain the final product 45. The painting of intermediate 44 (not separated) and subsequent dehydrogenation have been performed under reaction conditions. Scheme 15

85585 45 • 74-44 200307684 As depicted in Scheme 16 below, the substituents on the benzene ring can be introduced from their corresponding bromo compounds via a Suzuki coupling reaction with a Buchwald coupling reaction. The bromine-substituted compound 47 is prepared by direct bromination of NBS via compound 46 or from commercially available tryptamine. Compound 47 was used in a Suzuki coupling reaction with dihydroxyborane (Miyaura et al., C / z side · 1995, 9 Yun, 2457-2483) to obtain the aryl substituted product 48, and the Buchwald coupling reaction (Wolfe Et al., / Org. C / zem. 2000, (55, 1144-1157), to obtain the amine-substituted product 48. Scheme 16

As depicted in Figure 17 below, the conversion of the functional group can be achieved on the benzene ring. The oxygen on the 49 benzene ring and the protecting group on the nitrogen atom such as an alkyl group are removed, and other groups are introduced to form 51 through a reaction such as the alkylation and tritiation of 50. 85585 75- 200307684 Scheme 17 R6 R7f

X = NH or 〇 pg = protecting group

Alkylation --► or fermentation r45 r8xCc ^^ Rr3

H C02Et 51

As depicted in Figure 18 below, 1-keto compound 53 can be used as a key intermediate to other functional groups. 1-keto compound 53 is made by the oxidation of DD (and its reduction to obtain the corresponding alcohol 54. 54 is treated with tri | methanesulfonic anhydride to form trifluoromethanesulfonate 55, which is not It is separated and treated with RXH (alcohols, thiols, and amines) to obtain the compound Hong. The famous compound 53 is dimethylphenyl dream roast, and when treated in TFA, only the product 57 is removed to remove the product 57 , Alcohol 54 is an intermediate. It is also treated with ethylene glycol toluic acid under reflux to form a compound ^ 85585 76- 200307684 Scheme 18 R8II-: l]

N-RJ H CO, Et 52

〇 DDQ

NaBH3CN RXH

HO

Tf2〇

Tf〇

RX

3 r8 (XCn-r H C02Et 57

PhMe2SiH 53-

TFA, 60 ° C As depicted in Figure 19 below, carboline 60 is cyclized by tryptophan-spengler derivatives of tryptamine derivatives and aldehydes (Cox and Cook, CAem. 1995, 95, 1797-1842), Then it is made by the effect of 59. Scheme 19

68 59 60 85585 -77- 200307684 The pharmaceutical composition provided by this pharmaceutical composition contains a therapeutically effective amount of one or more nuclear receptor activity modulators provided herein, which can be used for prevention, treatment Or improve one or more symptoms or diseases associated with nuclear receptor activity including farnesin x receptor and / or orphan nuclear receptor activity. Such diseases or conditions include, but are not limited to, hypercholesterolemia, hyperlipoproteinemia, hypertriglyceridemia, dyslipidemia, hyperglycemia, diabetes, dyslipidemia, atherosclerotic disease events, Stone disease, acne vulgaris, acne-like skin symptoms, type II diabetes, Parkinson's disease, cancer, Alzheimer's disease, inflammation, immunological disorders, lipid disorders, obesity, and features that disrupt epidermal barrier function Symptoms, hyperlipidemia, bile stagnation, peripheral occlusive disease, hemorrhagic stroke, symptoms of disrupted differentiation or hyperplasia of the epidermis or mucosa, and heart and vascular disorders. Furthermore, the pharmaceutical composition provided herein contains a therapeutically effective amount of one or more nuclear receptor activity modulators provided herein, which can be used to prevent, treat or ameliorate one or more symptoms of a disease or disorder, which It is not directly related to nuclear stylistics, but complications of its disease or condition can be treated with the requested compounds and compositions. For example, but not limited to, gallbladder fibrosis is typically not associated with nuclear receptor activity, but can cause bile stagnation, which can be treated with the subject compounds and compositions. These compositions contain one or more compounds provided herein. The compound is preferably formulated into appropriate pharmaceutical preparations, such as solutions, suspensions, tablets, dispersible tablets, pills, capsules, powders, sustained release formulations or elixirs, for oral administration, or for parenteral administration. For administration in sterile solutions or suspensions 85585 -78- 200307684 ', as well as transdermal patch preparations and dry powder inhalers. Typically, the above compounds are formulated into pharmaceutical compositions using techniques and procedures known in the art (see, for example, this / 萦 表 痳 # 麦 式, fourth edition 1985, 126). In these compositions, an effective concentration of one or more compounds or pharmaceutically acceptable derivatives is mixed with an appropriate pharmaceutical carrier or vehicle. These compounds can be derivatized to their corresponding salts, esters, associated ethers or esters, acids, bases, solvates, hydrates or prodrugs before formulation, as described above. The concentration of the compound in the composition, when administered, effectively transmits an amount to treat, prevent, or ameliorate one or more symptoms of a disease or condition associated with or involved in nuclear receptor activity. Such diseases or conditions include, but are not limited to, hypercholesterolemia, hyperlipoproteinemia, hypertriglyceridemia, fat metabolism disorders, hyperglycemia, diabetes, dyslipidemia, atherosclerotic disease events, gallstone disease Acne vulgaris, acne-like skin symptoms, type 11 diabetes mellitus, Parkinson's disease, cancer, Alzheimer's disease, inflammation, immunological disorders, lupus disorders, obesity, and features that disrupt epidermal barrier function Symptoms, hyperlipidemia, bile depression / peritoneal occlusion disease, hemorrhagic stroke, symptoms of disrupted differentiation or hyperplasia of the epidermis or mucosa, and heart and vascular disorders Typically, these compositions are formulated for single-dose administration. In order to formulate the composition, the weight fraction of the compound is dissolved, suspended, dispersed, or mixed in other ways at the selected medium, at the effective concentration, so that the treated symptoms are relieved or improved. Suitable for administration of the compounds provided herein < medical carriers or vehicles, including any such vehicle known to those skilled in the art to be suitable for a particular administration. 85585 -79- 200307684 In addition, the compounds may be formulated in the composition as individual pharmaceutically active ingredients, or may be combined with other active ingredients. Microlipid suspensions, including tissue-targeted liposomes, such as tumor-targeted liposomes, are also suitable as pharmaceutically acceptable carriers. It can be prepared according to methods known to those skilled in the art. For example, microlipid formulations can be prepared as described in U.S. Patent 4,522,811. Briefly, microlipids, such as multilayer vesicles (MLv), can be formed by drying lecithin donkey choline and cerebrolipid serine (7.3 mol ratio) on the inside of the flask. Add a solution of the compound provided herein in phosphate-salt-buffered saline (PBS) lacking divalent cations, and shake the flask until the lipid membrane is dispersed. The formed vesicles were washed to remove the uncoated compound 'and pelletized by centrifugation, and then resuspended in PBS. The active compound is contained in a pharmaceutically acceptable carrier in an amount sufficient to exert a therapeutically effective effect on the treated patient in the absence of undesirable side effects. Therapeutic effective concentrations can be empirically determined by testing compounds in in vitro and in vivo systems described herein and in International Patent Application Publications 99/27365 and 00/25134 and then extrapolating from them to obtain human doses. And measured. The concentration of the active compound in the pharmaceutical composition depends on the absorption, inactivation, and excretion rates of the active compound, the physicochemical characteristics of the compound, the time schedule of dosage and the amount administered, and other factors known to those skilled in the art. For example, the amount delivered is sufficient to ameliorate one or more symptoms of a disease or condition related to, or in which nuclear receptor activity is implicated, as described herein. Typically, a therapeutically effective dose should produce a serum concentration of the active ingredient in the range of about 85585 -80-200307684 0.1 μg / ml to about 50-100 μg / ml. These pharmaceutical compositions should typically provide a dosage of about 0.001 mg to about 2000 mg of compound per kg of body weight per day. Pharmaceutical dosage unit forms are prepared to provide from about 1 to about 1000 mg, and preferably from about 10 to about 50 mg of the required active ingredient or combination of necessary ingredients per dosage unit form. The active ingredients may be administered simultaneously or may be divided into many smaller doses to be administered at time intervals. It should be understood that the precise dose and duration of treatment are a function of the disease being treated and can be determined empirically using known test protocols or extrapolating from in vivo or in vitro test data. It should be noted that the concentration and dose values may also vary with the severity of the symptoms to be reduced. It should be more clear that for any particular patient, the specific dosage should be used according to individual needs and the professional judgment of the person who administered or administered the composition, adjusted over time 'and the concentration ranges presented herein are only examples Is not intended to limit the scope or implementation of the requested composition. Pharmaceutically acceptable derivatives include acids, bases, alcohol ethers and esters, salts, esters, hydrates, solvates, and prodrug forms. The Yanchun biological system was selected so that its pharmacokinetic properties were better than its corresponding neutral compound. Thus' the effective concentration or amount of one or more of the compounds described herein or their musically acceptable derivatives is mixed with a suitable pharmaceutical carrier or vehicle for systemic, topical or regional administration to form a pharmaceutical combination Thing. The compound is added in an effective amount to improve one or more of the symptoms or treatment or prevention of a disease or condition in which nuclear receptor activity is implicated or involved in nuclear receptor activity as described herein. The concentration of the active compound in the composition depends on the absorption, inactivation, excretion rate of the active compound 85585 -81-200307684, the dosage schedule, the amount to be administered, the specific formulation, and other factors known to the skilled artisan set. These compositions are intended to be administered by appropriate routes including oral, parenteral, rectal, topical and regional. Capsules and tablets are currently preferred for oral administration. The composition is in liquid, semi-liquid or solid form ' and is formulated in a manner suitable for each route of administration. Preferred modes of administration include parenteral and oral modes of administration. Oral administration is currently the best. Solutions or suspensions for parenteral, intradermal, subcutaneous or topical application may contain any of the following ingredients: sterile diluents such as water for injection, saline solution, non-volatile oil, polyethylene glycol, glycerol, propylene glycol or other synthetics Solvents, biological agents such as methanol and parabens; antioxidants such as ascorbic acid and sodium bisulfite; chelating agents such as ethylene diamine tetraacetic acid (EDTA); buffers such as acetate , Citrate and phosphate; and withering permeability < acting agents, such as sodium chloride or dextrose. Parenteral preparations can be contained in ampoules made of glass, plastic or other suitable materials, disposable > king shots or single or multiple dose vials. In cases where the compound exhibits insufficient solubility, a method that promotes the bathing of the compound can be used. This method is known to those skilled in the art and includes, but is not limited to, the use of co-dropping agents, such as dimethylformamides 〇), use a surfactant, such as TWEEN®, or dissolve in aqueous sodium bicarbonate solution. Derivatives of chelating substances, such as compound precursor drugs, can also be used to formulate effective pharmaceutical compositions. When the compound is mixed or added, the resulting mixture may be a solution, a suspension 85585 -82- 200307684 liquid, an emulsion or the like. The form of the resulting mixture will depend on many factors, including the mode of intended administration and the solubility of the compound in the selected carrier or vehicle. Effective concentrations are sufficient to ameliorate the symptoms of the disease, disorder or condition being treated, and can be determined empirically. These pharmaceutical compositions are provided in unit dosage forms for administration to humans and animals, such as tablets, capsules, pills, powders, granules, sterile parenteral solutions or suspensions and oral solutions or suspensions, and oils. -An aqueous emulsion containing an appropriate amount of a compound or a pharmaceutically acceptable derivative thereof. Pharmaceutically active compounds and their derivatives are typically formulated and administered in unit or multiple dose forms. A unit dosage form as used herein means a physically separate unit suitable for use in human and animal patients, and individually packaged, as known in the art. Each unit dose contains a predetermined amount of a therapeutically active compound sufficient to produce the desired therapeutic effect, along with the required pharmaceutical carrier, vehicle or diluent. Examples of unit dosage forms include ampoules and syringes, and individually packaged tablets or capsules. Unit dose forms can be administered in fractions or multiples. Multiple-dose forms are many identical unit-dose forms that are packaged in a single container and intended to be administered as separate unit-dose forms. Examples of multiple dose forms include vials, tablets or capsules or pints or gallons. Therefore, multiple dose forms are in multiple unit doses' which are not separated in the package. This composition may be accompanied by an active ingredient: a diluent, such as lactose, sucrose, dicalcium phosphate or carboxymethyl cellulose; a lubricant, such as magnesium stearate, calcium dibasic acid and talc; and a binder, such as Starch, natural gums, such as acacia, gelatin, glucose, molasses, polytetramethylene, biloxone, 85585 -83- 200307684 cellulose and its 彳 1 organism, wave phase _dGne), cross-linked povidone (crospovidone) Other such adhesives known to those here. Liquid pharmaceutically-administrable compositions can be prepared, for example, in the following manner, so that , Dissolve, disperse or mix in other carriers in the carrier, such as water, saline, dextrose aqueous solution, glycerol-alcohol, ethanol, etc., then form a solution or a liquid. If necessary, it is to be administered The pharmaceutical composition may also contain a small amount of non-toxic auxiliary substances, such as wetting agents, emulsifiers or solubilizers, granules, etc., such as cool salts, sodium clavulanate, cyclodextrin derivatives, monolauric acid flowers Caramel, Triethanolamine Sodium Acetate , Triethanolamine oleic acid, and other such agents. The actual method for preparing this dosage form is known to or will be understood by those skilled in the art; for example, see Remington's Medical Science, Secret Publishing Company Tao. n, pa) "15th edition, 1975. The composition or formulation to be administered will, in any event, contain an amount of active compound sufficient to reduce the symptoms of the patient being treated. A dosage form or composition may be prepared which contains the active ingredient in the range of 0. to.% While the remainder consists of a non-toxic carrier. For oral technologies 5 'Pharmaceutically acceptable non-toxic compositions are shaped by incorporating any of the commonly used excipients &' e.g. pharmaceutical grades of mannitol, lactose, flour powder, magnesium crescent , Talc, cellulose derivatives, crosslinked sodium methylcellulose, glucose, sucrose, magnesium carbonate or saccharin sodium. Such compositions include solutions, suspensions, tablets, capsules, powders, and sustained release formulations such as, but not limited to, implants and microencapsulated delivery systems, and biodegradable, biocompatible polymers' For example, collagen, acetic acid, ethyl acetate, polyhepatic, polyglycolic acid, polyorthoic acid, polylactic acid, and others. Methods for preparing these compositions 85585-84-200307684 are known to those skilled in the art. Compositions intended to be covered may already have 0.001% -100% active ingredients, preferably 0.1-85%, and typically 75-95%. These active compounds or pharmaceutically acceptable derivatives can be formulated as carriers to protect the compounds against rapid self-exclusion, such as time-release formulations or coatings. These compositions may contain other active compounds to obtain a combination of desired properties. The compounds provided herein or their pharmaceutically acceptable derivatives, as described herein, can also be advantageously administered with another pharmacological agent for therapeutic or prophylactic purposes, which pharmacological agent has been It is known to be valuable for treating one or more of the diseases or conditions cited above, such as diseases or conditions associated with or in which nuclear receptor activity is implicated. It should be understood that such combination therapies constitute another aspect of the compositions and methods of treatment provided herein. L Composition for oral administration The oral pharmaceutical dosage form is either solid, gel or liquid. The solid dosage forms are tablets, capsules, granules and bulk powder. Types of oral tablets include compressed, chewable lozenges, and tablets that can be enteric-coated, sugar-coated, or film-coated. Capsules can be hard or soft gelatin capsules, while granules and powders can be provided in a non-foamed or foamed form with other ingredients known to those skilled in the art. In some embodiments, the formulation is a solid dosage form, preferably a capsule or tablet. Tablets, pills, capsules, lozenges, etc. can be ancient. Any of the following ingredients or similar compounds: binders; thinners; disintegrants; lubricants; glidants; sweeteners; and flavoring agents. Examples of the binder include microcrystalline cellulose, tragacanth gum, grape soluble 85585 -85- 200307684 solution, arabic gum solution, gelatin solution, recommended sugar, and rice flour paste. Lubricants include talc, powder, stearic acid, or stone, pine and stearic acid. Diluents include, for example, lactose, sucrose, starch, kaolin, s, mannitol, and diphosphate. Help n1] includes, but is not limited to, colloidal silica. Disintegrants include cross-linked sodium methyl cellulose, sodium starch glycolate, alginic acid, rice starch, potato starch, bentonite, methyl cellulose, agar, and carboxymethyl cellulose. Colorants include, for example, any certified water-soluble FD and C dyes, mixtures thereof; and water-insoluble dyes, suspended on alumina hydrate #. Sweeteners include sucrose, lactose, mannitol and artificial sweeteners such as saccharin and any number of spray-dried flavors. Flavoring agents include natural flavors extracted from plants, such as natural shellfish, and 60% of Chinese firs that produce pleasant sensations, such as, but not limited to, mint and methyl salicylate. Wetting agents include propylene glycol monostearate, anthocyanin monooleate, diethylene glycol monolaurate, and polyoxyethyl lauryl ether. Enteric coatings include fatty acids, fats, waxes, shellac, ammoniated shellac, and cellulose acetate phthalate. Thin film coatings include hydroxyethyl cellulose, sodium carboxymethyl cellulose, polyethylene glycol 4000 φ, and cellulose acetate urate. If oral tonic is desired, the compound may be provided in a composition that protects it from the acidic environment of the stomach. For example, the composition can be formulated in an enteric coating ' to maintain its integrity in the stomach and release the active compound in the intestine. The composition can also be formulated with antacids or other such ingredients. When the dosage unit form is a capsule, it may contain, in addition to materials of the above type, a liquid carrier such as a fatty oil. In addition, the dosage unit form can contain 85585 -86-200307684 various other substances that modify the physical form of the dosage unit, such as coatings for sugar and other enteric solvents. This compound can also be administered as an ingredient in elixirs, suspensions, syrups, tablets, dusters, chewing gum or the like. In addition to the active compounds, syrups can contain sucrose as a sweetener, as well as certain preservatives, dyes, and colorants and flavors. It is also possible to mix this active substance with other active substances that do not damage the intended action, or with supplementary substances, such as antacids, H2 blockers and diuretics. The active ingredient is a compound as described herein or a pharmaceutically acceptable derivative thereof. Higher concentrations of up to about 98% by weight of active ingredient can be added. The pharmaceutically acceptable carriers included in the tablets are binders, lubricants, diluents, disintegrating agents, i-coloring agents, flavoring agents, and wetting agents. The enteric solvent-coated tablet, because of the enteric solvent coating, resists the action of gastric acid and disintegrates or disintegrates in the neutral or alkaline intestines. Sugar-coated tablets are compressed tablets that are coated with several different pharmaceutically acceptable substances. Film-coated tablets are compressed tablets, which have been coated with a polymer or other suitable coating. Multi-encapsulation tablets are the above-mentioned acceptable substances. Compressed tablets made by more than one compression cycle can also be used; Flavoring and sweetening agents are used in compressed tablets, sugar coatings, multiple compressions and tabletting. Scaling and sweetening agents are particularly useful for forming p-able and chewable tablets and lozenges. Or a form of the dosage form I includes an aqueous solution, an emulsion, a suspension, a solution and a suspension prepared from non-foaming particles and a foaming back prepared from the foaming particles. Aqueous solutions include, for example, elixirs and syrups. Emulsions are either oil in 85585 -87- 200307684 water type or water in oil type. Tinctures are transparent, sweetened, and hydroalcoholic preparations. Pharmaceutically acceptable carriers used in elixirs include solvents. Syrup is a concentrated aqueous solution of sugar, such as sucrose, and may contain preservatives. Emulsions are two-phase systems in which one liquid is dispersed as small spheres throughout the other. Pharmaceutically acceptable carriers used in emulsions are non-aqueous liquids, emulsifiers and preservatives. Suspensions use pharmaceutically acceptable suspending agents and preservatives. Pharmaceutically acceptable substances for use in non-foaming granules to be reconstituted into a liquid oral dosage form, including diluents, sweeteners, and wetting agents. Pharmaceutically acceptable substances for use in foaming granules to be reconstituted into a liquid oral dosage form, including sources of organic acids and carbon dioxide. Coloring and flavoring agents are used in all of the above dosage forms. Solvents include glycerin, anthocyanin, ethanol, and syrup. Examples of preservatives include glycerol, methyl and propyl parabens, benzoic acid adducts, sodium benzoate, and alcohols. Examples of non-aqueous liquids used in emulsions include mineral oil and cottonseed oil. Examples of emulsifiers include gelatin, gum arabic, tragacanth gum, bentonite, and surfactants, such as polyethylene oxide monooleate anthocyanin polysaccharide. Suspensions include sodium carboxymethylcellulose, pectin, tragacanth gum, Veegum and gum arabic. Diluents include lactose and sucrose. Sweeteners include sucrose, syrup, glycerin, and artificial sweeteners such as saccharin. Wetting agents include propylene glycol monostearate, anthocyanin monooleate, diethylene glycol monolaurate, and polyethylene oxide lauryl ether. Organic acids include citric and tartaric acids. Sources of carbon dioxide, including sodium bicarbonate and sodium carbonate. Colorants include any approved water-soluble FD and C dyes, and mixtures thereof. Flavoring agents 85585 -88-200307684 include natural flavors extracted from plants such as fruit, and synthetic blends of compounds that produce a pleasant taste. For solid dosage forms, the solution or suspension, for example in propylene carbonate, vegetable oil or triglyceride, is preferably coated in a gelatin capsule. Such a mixture is prepared in U.S. Patent Nos. 4,328,245; 4,409,239; and 4,410,545. For liquid dosage forms, this solution, for example in polyethylene glycol, can be diluted with a sufficient amount of a pharmaceutically acceptable liquid carrier such as water to be easily measured for administration. Alternatively, liquid or semi-solid oral formulations may be prepared by dissolving or dispersing the active compound or salt in vegetable oils, glycols, triglycerides, propylene glycol esters (such as propylene carbonate), and other such carriers, and The solution or suspension is coated in hard or soft gelatin capsule shells. Other useful formulations include those described in U.S. Patents 28,819 and 4,358,603. Briefly, such formulations include but are not limited to containing compounds provided herein, dialkylated mono- or polyalkanediols, including, but not limited to, 2-dimethoxymethane, diethylene glycol Monomethyl ether, triethylene glycol dimethyl ether, tetraethylene glycol dimethyl ether, polyethylene glycol-350_monomethyl ether, polyethylene glycol_55〇_dimethyl ether, polyethylene glycol · 75 〇_ Monomethyl ether, where 350, 550 and 750 refer to the approximate average molecular weight of polyethylene glycol and one or more antioxidants, such as butylated hydroxytoluene (ΒΗΤ), butylated hydroxytoluene (ΒΗΑ) ), Propyl gallate, vitamin E, hydroquinone, hydroxyvanillin, ethanolamine, lecithin, cerebral phospholipid, ascorbic acid, malic acid, anthocyanin, phosphoric acid, thiodipropionic acid and its esters, and two Thiamate. Other formulations include, but are not limited to, alcoholic aqueous solutions, including pharmaceutically acceptable 85585 -89-200307684 acetals. The alcohols used in these formulations are any pharmaceutically acceptable water-miscible solvents having one or more hydroxyl groups, including but not limited to propylene glycol and ethanol. The acetals include, but are not limited to, the second (lower alkyl) acetals of lower alkyl aldehydes such as acetaldehyde diethyl acetal. In all embodiments, the tablet and capsule formulations can be applied in a manner known to those skilled in the art to modify or maintain dissolution of the active ingredient. Therefore, for example, they can be coated with intestinal digestible coatings such as phenylsalicylate, waxes and cellulose acetate phthalate. 2. Dosage, lysate, and sacrifice_ Parenteral administration, which is generally characterized by injection, whether subcutaneous, intramuscular, or intravenous, is also intended to be included herein. Injectables can be made in a white form, either as a liquid solution or suspension, suitable for injection as a solid form dissolved or suspended in a liquid, or as an emulsion. Peripheral excipients are, for example, water, saline, dextrose, glycerol or ethanol. In addition, the pharmaceutical composition to be administered may contain a small amount of non-toxic auxiliary substances such as wetting or emulsifying agents, pH buffering agents, stabilizers, solubility enhancers, and other such agents, such as sodium acetate. , Monolaurate anthocyanin vinegar, triethanolamine oleate and cyclodextrin. Implantation of a slow-release or sustained-release system such that a constant amount of dose is maintained (see, e.g., U.S. Patent 3,710,795) is also intended to be included herein. In short, the compounds provided herein are dispersed in a solid internal matrix, such as polymethyl methacrylate, polybutyl methacrylate, plasticized or unplasticized polyvinyl chloride, plastic Plasticized nylon, plasticized polyethylene terephthalate, natural rubber, polyisoprene, polyisobutylene, 85585 200307684 poly% 'polyethylene, ethyl acetic acid acetic acid copolymer, Polyammonium rubber, water-based siloxane, polysiloxane copolymer, hydrophilic polymers such as acrylic acid and hydrolysate hydrogels, collagen, cross-linked polyethylene glycol and cross-linking Partially hydrolyzed polyethylene acetate, which is surrounded by external polymeric films, such as polyethylene, polypropylene, ethylene / propane copolymer, ethylene / ethyl propionate copolymer, ethyl acetate / ethyl acetate Copolymer, Silicone Rubber, Polydiene, Oxide, Polychloroprene Rubber, Chlorinated Polyethylene, Polyvinyl Chloride, Ethyl Chloride Copolymer with Acetyl Acetate, Dichloromethane Ethylene, propylene glycol, ionomer polyethylene terephthalate, butyl rubber, epichlorohydrin Fascine acetate / ethylene copolymer material, associative acetate / vinyl acetate associative stuffed / ethyl acetate broom and broom alcohol terpolymer / copolymer B associative yloxy ethanol, which is insoluble in body fluids based. In the release rate control step, the 'compound is exuded through the outer hydration film. The percentage of active compound included in such parenteral compositions is highly dependent on its specific properties, the activity of the compound, and the needs of the patient. Parenteral administration of this composition includes intravenous, subcutaneous and intramuscular administration. Preparations for parenteral administration include 'sterile solutions prepared for injection, sterile dry cold product', such as dry powder, ready to be combined with solvents immediately before use, 'including subcutaneous tablets, sterile suspensions prepared for injection Prepare sterile dry insoluble products and sterile emulsions to be combined with the vehicle immediately before use. These solutions may be either aqueous or non-aqueous. If administered intravenously, suitable carriers include physiological saline or linalate (PBS), and these solutions contain thickening and solubilizing agents such as glucose, polyethylene glycol, and polypropylene glycol and mixture. 85585 -91- 200307684 Pharmaceutically acceptable carriers used in parenteral preparations, including aqueous vehicles, non-aqueous vehicles, antimicrobials, isotonic agents, buffers, antioxidants, local anesthetics, suspensions and Dispersants, emulsifiers, sequestering or chelating agents and other pharmaceutically acceptable substances. Examples of the aqueous vehicle include sodium chloride injection, Ringer's injection, isotonic dextrose injection, sterile water injection, dextrose and lactated Ringer's injection. Non-aqueous parenteral vehicles include non-volatile oils of vegetable origin, cottonseed oil, corn oil, sesame oil and peanut oil. Antimicrobials must be added to parenteral preparations packaged in multi-dose containers at bacteriostatic or fungal concentrations, including phenols or cresols, mercury agents, methanol, gas butanol, para-hydroxy Methyl benzoate and propyl ester, thimerosal, ammonium chloride and ethoxylate. Isotonicity agents include sodium chloride and dextrose. Buffering agents include phosphate and citrate. Antioxidants include acidic sodium sulfate. Local anesthetics include procaine hydrochloride. Suspensions and dispersants include sodium carboxymethylcellulose, isopropylcellulose and polyvinyltetrahydropyrrolidone. Emulsifiers include TWEEN® 80. Sequestering or chelating agents of metal ions include edta. Pharmaceutical carriers also include ethanol, polyethylene glycol and propylene glycol, water soluble solvents, and sodium hydroxide, hydrochloric acid, citric acid or lactic acid for pH adjustment. The concentration of the pharmaceutically active compound is adjusted so that the injection solution provides an effective amount to produce the desired pharmacological effect. The exact dose depends on the age, weight and symptoms of the patient or animal, as known in the art. Unit-dose parenteral preparations are packaged in ampoules, vials or syringes with needles. All preparations for parenteral administration must be sterile, as known and practiced in the art. 85585 -92- 200307684 Explanation: Intravenous or intraarterial infusion of a sterile aqueous solution containing an active compound is an effective mode of administration. Another embodiment is a sterile aqueous or oily solution or suspension containing the active substance, which is injected as needed to produce the desired pharmacological effect. Injectables are designed for local and systemic administration. Typically, a therapeutically effective dose is formulated to contain the active compound at a concentration of at least about 0.01% w / w up to about 90% w / w or more, preferably more than 丨% w / w. Organization. The active ingredients may be administered simultaneously or may be divided into a number of smaller doses' to be administered at time intervals. It should be understood that the precise dose and duration of treatment is a function of the tissue being treated and can be determined empirically using known test protocols or extrapolation from in vivo or in vitro test data. It should be noted that the concentration and dose values may also vary with the age of the individual being treated. It should be more clear that, for any specific patient, the specific dosage and usage should be adjusted according to individual needs and the professional judgment of the person who executes or manages the formula. The concentration range proposed in this article is only an example. It is not intended to limit the scope or implementation of the requested formulation. This compound may be micronized or suspended in another suitable form, or it may be derivatized to produce a more active product or a prodrug. The form of the resulting mixture depends on a number of factors, including the intended mode of administration and the solubility of the compound in the selected carrier or vehicle. The effective concentration is sufficient to ameliorate the symptoms of the symptoms' and can be determined empirically. 3. Freeze-dried powder bundles In this article, ‘we are also interested in dry powders, which can be reconstituted into liquids, emulsions, and other mixtures for administration. It can also be reconstituted and formulated as a solid or a gel with 85585 -93- 200307684. Bacteria supply; Donggan powder is prepared by dissolving the compound provided herein or a pharmaceutically acceptable derivative thereof in a suitable solvent. This solvent may contain excipients that improve the stability or other pharmacological ingredients of the powder or a reconstituted solution made from the powder. Excipients that can be used include, but are not limited to, dextrose, anthositol, fructose, maize syrup, xylitol, glycerol, glucose, sucrose, or other suitable agents. This solvent may also contain buffers such as citrate, sodium or potassium phosphate, or other such buffers known to those skilled in the art, typically at about neutral pH. This solution is then sterile filtered under standard conditions known to those skilled in the art, followed by lyophilization, to provide the desired formulation. Generally, the resulting solution is dispensed into a vial for lyophilization. Each vial will contain a single dose (10-100 mg, preferably 100-500 mg) or multiple doses of the compound. The lyophilized powder may be stored under appropriate conditions, such as at about 4 ° C to room temperature. — This lyophilized powder is reconstituted with water for injection. It is provided for parenteral administration. For reconstitution, about MO mg, preferably 5 to 35 mg, and more preferably about 9 to 30 mg of powder per milliliter of sterile water or equivalent thereof is added. The exact amount depends on the compound chosen. ^ Way to decide. Lessons Learned 4. Housing Department Administration Bureau Shao mixtures are made as described for local and systemic administration. The resulting mixture can be a solution, suspension, emulsion, or the like, and is adjusted to a cream, gel, ointment, emulsion, solution, sensitizer, lotion, sensible hydration solution, ST agent, Pastes, foams, aerosols, compliance solutions, mouth sprays: 85585 -94- 200307684 agents, bandages, skin patches or any other formula suitable for topical administration. 〇 Formulate the mouthpiece or a pharmaceutically acceptable derivative thereof into an aerosol for local use, such as by inhalation (see, e.g., U.S. Patent Nos. 4,044,126, 4, and 4,364,923, which describe the transport of steroids Aerosols, which can be used to treat inflammatory diseases, especially asthma). These formulations for administration to the respiratory tract may be in the form of aerosols or solutions for nebulizers or as fine powders for insufflation: alone or in combination with an inert carrier such as lactose. In this case, the particles (typically have a diameter of less than 50 microns, preferably less than ㈣

Meter. W mouthwash can be formulated for regional or local application, such as topical application to the skin and mucous membranes, such as in the form of gels, creams, and lotions in clear eyes, for prescription to clear eyes, Or for coating in the cistern or spinal canal. Topical administration is intended to cover transdermal delivery ' as well as administration to the eyes or mucous membranes, or for inhalation therapy. The active compound may also be administered alone or in combination with nasal solutions of other pharmaceutically acceptable excipients. These solutions, especially those intended for eye users, can be formulated with appropriate salt to produce a #%-10% isotonic solution with a pH of about 5-7. 5. The i-AA route of administration, such as tincture, and other routes of administration, such as local application, transdermal patch, and rectal administration, is also intended to be included in this article. Transdermal patches, including iontophoresis and electrophoresis devices, are well known to those skilled in the art. For example, this type of patch is disclosed in U.S. Patent Nos. 6,267,983, 6,261,595, 6'256,533, 6,16 and 301,6, 〇24,975,6, Cong 5, 5,985, which is taken as 5,860,957. 85585 -95- 200307684 A medicinal dosage form for rectal administration. It is a rectal test, capsule and tablet to provide systemic action. 4 Intestinal suppositories are used herein to mean solid objects inserted into the rectum that will melt or soften at body temperature, releasing one or more pharmacologically or therapeutically active ingredients. Pharmaceutically acceptable substances used in rectal suppositories are bases or vehicles, and agents that increase the melting point. Examples of the base include cocoa butter (cocoa bean oil), glycerin-gelatin, carbon wax (polyoxyethylene glycol), and suitable fatty acid-based glycerol mono-, di-, and tri-esters. Combinations of different bases can be used. Agents that increase the melting point of suppositories include whale wax and wax. Rectal suppositories can be made either by compression or by molding. Rectal suppositories typically weigh about 2 to 3 grams. Tablets and capsules for rectal administration are made using the same pharmaceutically acceptable substances as for the formulations for oral administration, and made by the same method. 6. Target Formulation The compounds provided herein or their pharmaceutically acceptable derivatives may also be formulated to target specific tissues, recipients or other areas of the body of the patient to be treated. Many of these methods of targeting are known to those skilled in the art. All such methods of targeting are intended to be included herein'for use in the compositions of the present invention. Non-limiting examples of methods of targeting can be found in, for example, U.S. Patent No. 6,316,652,6,274,552,6,271,359,6,253,872, 6,139,865, 6,131,570, 6,120,751, 6,071,495, 6,060,082, 6,048,736, 6,039,975, 6,004,534, 5,985,307, 5,972,366, 5,900,252, 5,840,674, 5,759,542 and 5,709,874. In a specific embodiment, the liposome suspensions include tissue-targeted liposomes, such as tumor-targeted liposomes, which are also suitable as acceptable carriers for pharmacy 85585-96-200307684. It can be prepared according to methods known to those skilled in the art. For example, microlipid formulations can be prepared as described in US Patent 4,522,811. # The microfat granules, such as multilayer vesicles (MLV), can be shaped by drying egg scale fat = alkali and cerebrolipid serine (7: 3 mole ratio) on the inside of the flask:: Add A solution of the compound provided in this solution in scale acid Buffered Saline (PBS) lacking divalent cations, and the flask was shaken until the lipid film: loose j. The formed vesicles were washed to remove the uncoated compound: ′ Granulated by centrifugation and resuspended in PBS. 7. Products into which these compounds or pharmaceutically acceptable derivatives can be packaged into products containing packaging materials, the compounds provided herein or their pharmaceutically acceptable; < Hob's effective modulation Body activity, including farnesin X receptors and / or orphan nuclear receptors, or for the treatment, prevention or amelioration of diseases that are mediated by nuclear receptors including farnesin X receptors and / or orphan nuclear receptors or Disorders, or implicated nuclear receptor activities in dragons, including farnesin x receptor and / or orphan nuclear receptor sex < disease or condition-or multiple symptoms, placed in packaging material, and labeled 'indicate that Compounds or compositions or pharmaceutically acceptable derivatives thereof are used to make nuclear receptors including farnesin x receptors and / or orphan nuclear receptors: or for / σ therapy, prevention or improvement of nuclear receptors Diseases or conditions that include farnesin X receptors and / or orphan nuclear receptors, or diseases or conditions in which nuclear receptor activity is involved includes farnesin x receptors and / or orphan nuclear receptor activities One or more symptoms. , = The products provided by & China contain packaging materials. Packed pharmaceutical products are packed with materials, which are familiar to those skilled in the art. See, for example, U.S. Patents 85585-97-200307684, 5,323,907, 5,052,558, and 5,033,252. Examples of pharmaceutical packaging materials include, but are not limited to, blister packs, bottles, tubing, inhalers, pumps, bags, vials, containers, syringes, and any packaging materials suitable for the selected formulation and the intended mode of administration and treatment. A broad range of formulations of the compounds and compositions provided herein are intended to be included as a variety of therapeutic drugs for which the nuclear receptor activity involved includes farnesin X receptor and / or orphan nuclear receptor activity as symptoms Or cause of any disease or condition. E. Evaluation of Compound Activity Standard physiological, pharmacological, and biochemical procedures can be used to test compounds to identify those who have biological activity that modulate the activity of nuclear receptors including farnesin X receptors and / or orphan nuclear receptors. Such detection includes, for example, biochemical detection, such as combined detection, fluorescence polarization detection, and FRET-based co-activator reflection enhancement detection (see generally Glickman et al., 5iomo / ecw / ar * Scr⑽7 No · 1 3 -10 (2002)), and cell-based assays, including co-transfection assays, using LBD-Gal 4 chimeras and protein-protein interactions (see Lehmann et al., J. CAem., 272 (6) 3137 -3140 (1997). High-throughput screening systems are commercially available (see, for example, Zymark, Hopkinton, MA; Air Technology Industries, Mentor, OH; Beckman Instruments, Fullerton, CA; Precision Systems, Natick , MA), which enables these assays to be operated in high throughput mode. These systems typically automate the entire process, including all samples and reagents are aspirated by pipette, liquid distribution timed culture, and microplates are suitable for The last read in the detection detector. These configurable systems provide high throughput and quick start, as well as a high degree of flexibility and customizability 85585 -98 · 200307684. The manufacturer of this system It provides detailed proposals for various high-throughput systems. Therefore, for example, Zymark provides a technical bulletin describing screening systems that detect gene transcription, ligand binding, etc. No washing or liquid separation steps are required. Detection is better for such high-throughput screening systems, and includes biochemical detection, such as fluorescence polarization detection (see, for example, Owicki, Institute of Cww / iScreen, October 2000; 5 (5) · · 297 ) Sencan Proximity Detection (SPA) (see, for example, Carpenter et al., Methods Mol Biol 2002; 190: 31-49) and fluorescence resonance energy transfer (FRET) or time-resolved FRET-based co-activator reflection enhancement detection ( Mukherjee et al., J steroid BiochemMol Biol July 2002; 81 (3): 217-25; (Zhou et al. Mol Endocrinol October 1998; 12 (10): 1594-604). Generally speaking, this This detection can be performed using either the full-length receptor or via a ligand-binding functional site (LBD). In the case of the farnesin X receptor, the LBD contains the full-length sequential amino acids 244 to 472. If fluorescent Light-labeled ligands are available, and the fluorescent Polarization detection system to provide a test compound to bind the nuclear receptor of interest to embodiment I, which changes based on the measurement by a fluorescence polarization trace to identify ligands are the substituted compounds occurs. In addition, this approach can also be used to monitor the ligand-dependent association of fluorescently-labeled co-activated peptides on our nuclear receptors of interest to detect the binding of ligands to our nuclear receptors of interest. The ability of a compound to bind to a receptor or a heterodimer complex with RXR can also be measured in a homogeneous detection format by using the Splendid Proximity Test (SPA), which assesses that a compound can be known to have a known effect on the receptor. Affinity radiation indicates the degree of ligand competition. In this pathway, the radioactivity emitted by the 5-labeled 85585-99-200307684 compound is produced. When it is brought into close proximity to the scintillator bound to the nuclear receptor system, such as beads containing Ysi-copper, it will produce Optical signal. If the radiolabeled compound is replaced from the nuclear receptor, the amount of light emitted from the nuclear receptor-binding scintillator will be reduced, and this can be easily detected using a standard microplate liquid flash plate reader, such as Wallac Microbeta Device. The heterodimerization of farnesin X receptors and RXRa can also be monitored by resonance energy transfer (FRET) or time-resolved FRET measurements to monitor binding of compounds provided herein to farnesin X receptors or other Nuclear receptor capabilities. Both approaches are based on the fact that energy transfer from the donor molecule to the acceptor molecule occurs only when the donor and acceptor are in close proximity. Typically, the purified LBD of our nuclear receptor of interest is labeled with biotin, and then mixed with the stoichiometric pyrene-labeled streptomycin amino acid (Wallac), and the purified LBD of RXRa is appropriately fluoresceinized. Such as the CY5TM logo. Equal molar amounts of each modified LBD were mixed together and allowed to equilibrate for at least 1 hour before adding to the sample to be tested for affinity, either at a variable or constant concentration. After equilibration, the time-resolved fluorescent signal is quantified using a fluorescent plate reader. Then, the affinity of the compound can be estimated from the graph of the concentration of the added compound from the fluorescence. This approach can also be used to measure the ligand-dependent interactions of co-activated peptides with nuclear receptors to characterize the activator or antagonist activity of the compounds disclosed herein. Typically, the detection in this case involves the use of a recombinant glutathione-S-transferase (GST) -nuclear receptor ligand binding functional site (LBD) fusion protein, and derived from a co-activated peptide such as a steroid receptor The co-activator 1 (SRC-1) receptor interacts with the functional site, and a sequenced synthetic biotinylated peptide. 85585 -100- 200307684 Typically, GST-LBD is labeled with a tritium chelate (donor) via a tritium-labeled anti-GST antibody, and a co-activated peptide is linked via a streptavidin-biotin Allophycocyanin identification. In the presence of a nuclear receptor activator, this peptide was supplemented to gst_lbd, resulting in the close proximity of tadpoles to allophycocyanin, enabling energy to be transferred from tadpole chelate to allophycocyanin. When this complex is excited with light at 340 nm, the excitation energy absorbed by the plutonium chelate is transmitted to a part of the allophycocyanin group, causing emission at 665 nm. If the tritium chelate is not brought in close proximity to the other algal steroids, then there is little or no energy transfer, and the tritium chelate excitation will cause emission at 615 nm. Therefore, the intensity of light emitted at 665 nm is an indicator of the strength of the protein-protein interaction. The activity of a nuclear receptor antagonist can be measured by measuring the ability of a compound to competitively inhibit (think ICS 0) the activity of a nuclear receptor activator. In addition, 'multiple cell-based detection methods can be successfully used in screening tests' to confirm and analyze the specificity of the compounds of the present invention. These approaches include co-transfection detection, translocation detection, complementary detection, and the use of gene activation techniques to overexpress endogenous nuclear receptors. There are three basic variants of the co-transfection detection strategy: co-transfection detection using full-length nuclear receptors and co-transfection detection using chimeric nuclear receptors, including fusion of the ligand-binding functional site of our nuclear receptor of interest To heterologous DNA binding functional sites, and detection based on the use of two mammalian hybrid detection systems. This basic co-transfection test is based on co-transfection into cells expressing a plasmid to express the nuclear receptor of interest in the cell. This cell has a reporter plasmid 85585 -101-200307684 which contains a report Daughter genes whose expression is under the control of a DNA sequence capable of interacting with nuclear receptors (see, for example, U.S. Patents 5,071,773, 5,298,429, 6,416,957, WO00 / 76523). Treatment of transfected cells with a nuclear receptor activator will increase the transcriptional activity of the receptor, which is reflected by increasing the performance of the reporter gene, which can be measured by a variety of standard procedures. For receptors acting as heterodimers with RXR, such as farnesin X receptors, co-transfection detection typically involves the use of expression plasmids of both nuclear receptors of interest and RXR. Typical co-transfection tests require obtaining full-length nuclear receptors and providing appropriate response elements with sufficient screening sensitivity and specificity for nuclear receptors of interest to us. The following full-length previously described proteins that are suitable for co-transfection research and analysis of the genes encoded by the compounds described herein include the rat farnesin X receptor (Gene Bank Registration Number NM_021745), human farnesin X receptor (Gene bank registration number NM_005123), human RXRa (gene bank registration number NM_002957), human RXR / 3 (gene bank registration number XMJJ42579), human RXRT (gene bank registration number XMJJ53680), human LXRa (gene bank registration number NM_005693) , Human LXR / 5 (gene bank registration number NM_007121), human PPARa (gene bank registration number NMJJ05036), and human PPAR5 (gene bank registration number NM_006238). The reporter plasmid can be constructed using standard molecular biology techniques by placing a cDNA encoded by a reporter gene downstream of a suitable minimal promoter. For example, constructing a luciferase reporter plasmid can be performed by placing a firefly luciferase encoded by cDNA, adjacent to the promoter of the Thyroid Nucleus Thymus Nucleus Transcriptase (located at thorax 85585-102- 200307684 adenosine kinase nucleotide). Sequential nucleotide residues -105 to +51), which are sequentially linked to various response elements. Many methods for co-transfection of this expression and reporter plasmid are known to those skilled in the art and can be used for co-transfection detection to introduce the plasmid into the appropriate cell type. Typically, such cells will not endogenously express nuclear receptors that interact with response elements used in reporter plasmids. A number of reporter gene systems are known in the art and include, for example, a test phosphatase (Berger, J. et al. (1988) gene MJ-10; Kain, SR. (1997) Methods. Mol. Biol. 6149 -60), / 3-galactosidase (see, US Patent No. 5,070,012 issued to Nolan et al. On December 3, 1991 and Bronstein, I., et al., (1989) J. (1: 1 ^ 1111111111.3 丨〇111111. Health 99-111), chloramphenicol acetate transferase (see 01011111, et al., Mol Cell Biol. (1982) 2 1044-51), / 3-glucosidase, peroxidase, / 5 · Lactamidase (US Patents 5,741,657 and 5,955,604), catalytic antibodies, luciferase (US Patents 5,221,623; 5,683,888; 5,674,713; 5,650,289; 5,843,746) and natural fluorescent proteins (Tsien, RY ( 1998) Amiu. Rev. Biochem. Division 509-44). Using a chimera containing a ligand binding functional site (LBD) to a heterologous DNA binding functional site (DBD) of our nuclear receptor of interest will expand the cell basis Detection of variability in a manner that directs the activation of nuclear receptors in question to a defined DNA binding function Defined DNA binding elements for site identification (see WO95 / 18380). This test will expand cell-based co-transfection detection in cases where the biological response or screening window is unsatisfactory using natural DNA binding functional sites In general, this method is similar to using 85585 -103- 200307684 with basic co-transfection detection, but using chimeric constructs instead of full-length nuclear receptors. Like full-length nuclear receptors, transfection Cells treated with the stimulator of nuclear receptor LBD will increase the transcriptional activity of heterologous DNA binding functional sites, which is reflected by increasing the performance of reporter genes as described above. Typically, for this type of chimeric construct Is based on DNA binding functional sites derived from defined nuclear receptors, or derived from yeast or bacterial-derived transcriptional regulators such as GAL4 and members of the LexA / Umud superfamily. A third type of cell for screening compounds of the present invention is The basic test is a mammalian two-hybrid test, which measures the ability of a nuclear hormone receptor to interact with cofactors in the presence of a ligand (see, for example, US Patent US 5 (667,973, 5,283,173, and 5,468,614). This basic approach is to generate three plasmid constructs that allow the interaction of nuclear receptors with the interacting protein to be coupled to transcriptional readouts in living cells. The first construct is an expression plasmid for expressing a fusion protein, which contains an interaction protein, or a part of the protein contains an interaction functional site, and is fused to a GAL4DNA binding functional site. The second expression plasmid includes a nuclear receptor encoded by the DNA that is of interest to us, fused to a strong transcriptional activation functional site, such as VP16, and the third construct includes a reporter plasmid that contains a minimal promoter and GAL4 upstream Reporter gene of activation sequence. Once all three plasmids have been introduced into the cell, the encoded GAL4 DNA-binding functional site in the first construct allows the fusion protein to specifically bind to the GAL4 position upstream of the smallest promoter. However, because the GAL4DNA binding functional site typically does not have strong transcriptional activation properties when isolated, the performance of the reporter gene only occurs to a low degree. In the presence of the ligand, the nuclear receptor-VP16 fusion protein can bind to the GAL4 interaction protein fusion 85585 -104- 200307684 protein, and the agent W16 is closely linked to GAL4

The test error changes within 15%. Typically, detection is performed in triplicates, and changes are made within 6 times. Each experiment is typically repeated three or more times' with similar results. The activity of the reporter gene can be conveniently normalized to the internal control group and the data can be plotted as a multiple activation relative to untreated cells. The positive control compound (actuator) can be added with DMS0 as a high and low control group for normalizing the test data. Similarly, antagonist activity can be measured by determining the ability of a compound to competitively inhibit activator activity. In addition, compounds and compositions can be evaluated for their ability to increase or decrease the expression of genes known to be modulated in vivo by farnesin X receptors and other nuclear receptors, using Northern blotting, RTPCR, or oligonucleotide microarrays Analytical method to analyze milk eight content. Western-assay can be used to measure the performance of proteins encoded by the farnesin X receptor-targeted genes. Genes known to be regulated by farnesin X receptors include cholesterol 7 α-hydroxylase (CYP7A1), a rate-limiting enzyme in the conversion of cholesterol to bile acids, and a small heterodimer partner- 丨 (SHP4 ), Bile salt output pump (BSEP, ABCB11), tubule bile acid export protein, bovine bile acid 85585 -105- 200307684 steel common transport peptide (NTCP, SLC10A1) and intestinal bile acid binding protein (I_ BABP) 〇 On request Compounds are directly related to a variety of diseases, established animal models exist, and they can be used to further analyze and characterize the requested compound. These model systems include diabetic dyslipidemia using Zucker (fa / fa) rats or (db / db) mice, and apolipoprotein E-deficient mice (ApoO-/-) t spontaneous hyperlipidemia, Hyperlipidemia caused by low-density lipoprotein receptor-deficient mice (LDRi) diet, and Αρ〇Ε (-Λ) and LDL (-/-) mice were fed a Western-style diet (21% fat, 〇5% cholesterol). In addition, farnesin x receptors or LXR animal models (e.g., knocked out < mice) can be used to further evaluate the compounds and compositions of the invention in vivo (see, eg, Sinai et al., Ce //, 102: 731- 744 (2000), peer et al., Ce //, 93: 693-704 (1998)). — ~ Methods of using compounds and compositions The methods of using the compounds and compositions provided herein are also provided. These compositions are used to alter the nuclear

Farnesin X receptor activator, partial activator, partial antagonist or antagonist activity. The law system involves in vitro and in vivo use of compounds and combinations of object activity, including farnesin-like receptors and / or orphan nuclear receptors by providing the receptor with one or more compounds or combinations provided herein -200307684 'Physical exposure' to alter nuclear receptor activity including methods of farnesin x receptor and / or orphan nuclear receptor activity. Methods for reducing plasma cholesterol content and directly or indirectly modulating cholesterol metabolism, catabolism, synthesis, absorption, reabsorption, secretion or excretion are provided by administering the compounds and compositions as requested herein. Methods of using compounds and compositions to reduce dietary cholesterol absorption (see, for example, International Patent Application Publication 00/40965) are provided herein. Also mention

For use of the requested compounds and compositions to increase the performance of ATP-binding cassettes (ABCM), and thus a method of increasing reverse cholesterol transport in mammalian cells (see, for example, International Patent Application Publication WO 00/78972). Methods of reducing plasma triglyceride content and directly or indirectly modulating triglyceride metabolism, catabolism, synthesis, absorption, reabsorption, secretion or excretion are provided by administering the compounds and compositions provided herein as requested. • Reduce bile / decade and directly or indirectly modulate bile acid metabolism, catabolism, synthesis, adduction, reabsorption, secretion, excretion or bile acid pooling

Methods of mini-or composition are provided by administering the requested compounds and compositions provided herein. A method of treating, preventing, or ameliorating cholesterol, triglyceride, or bile acid content, or any combination thereof (a disease or condition), is provided using the compounds and compositions provided herein. Provided-some Methods to treat, prevent or ameliorate one or more symptoms of hyperlipidemia, hypercholesterolemia, dyslipidemia, and lipometabolism disorders, and to treat complications thereof. Hyperlipidemia a week refers to the abnormally high content of lipids present in In the blood 85585 -107- 200307684 Hyperlipidemia can be presented in at least three forms: 血 hypercholesterolemia, meaning South LDL cholesterol content (120 mg / gong and higher); (2) hyperglycemia in blood, Means high triglyceride content; (15 mg / combined and higher) and ⑺ combined with hyperlipidemia, meaning a combination of hypercholesterolemia and hypertriglyceridemia. '' Lipidemia disorders ,, The term refers to abnormal levels of lipoproteins in the plasma, including reduced and / or increased levels of lipoproteins (such as increased levels of low-density lipoprotein (LDL) and low-level protein (VLDL) ) And reduced levels of high-density lipoprotein (HDL) (less than 40 mg / gong)). Also to treat heart disease, prevent or improve atherosclerosis, atherosclerotic disease, atherosclerotic disease event And methods of one or more symptoms of atherosclerotic heart and vascular disease. Atherosclerosis is a process in which fatty deposits, cholesterol, cell waste products, calcium and other substances are accumulated in the inner lining of the artery. This accumulation is called a spot. It initially affects large and medium-sized arteries. Some arteriosclerosis often occurs when people are older. The spots may grow large enough to significantly reduce blood flow through the arteries. But significant damage to the body by radon can also occur when the arterial wall becomes brittle and ruptured. A ruptured atheromatous plaque may cause blood clots to form, which can block blood flow or separate and run to the body. Another part. If it happens and either of the blood clots blocks the blood vessels feeding the heart, it can cause a heart attack. If the blood clots block the blood that feeds the brain , It may cause a stroke. If the blood supplied to both arms or legs is reduced, it may cause difficulty walking and eventually gangrene. 85585 • 108- 200307684 Therefore, the atherosclerosis system covers a range of reasons Vascular diseases and symptoms of primary disease morphology. Atherosclerotic heart and vascular diseases can be detected and understood by physicians engaged in related medical fields, and include the following: restenosis after the vascular reformation procedure Coronary heart disease (also known as coronary heart disease or hemorrhagic heart disease), cerebrovascular disease, including hemorrhagic stroke, multiple infarct dementia, and peripheral vascular disease, including erectile dysfunction. Compounds of the present invention can be administered Or compositions to prevent or reduce the risk of coronary heart disease events, cerebrovascular events, and / or intermittent trekking or the risk of recurrence. Coronary heart disease events are intended to include coronary heart disease deaths, myocardial infarction, and coronary revascularization procedures. Cerebrovascular events are intended to include hemorrhagic or hemorrhagic stroke (also known as cerebrovascular accident) and transient hemorrhagic episodes. Intermittent trekking is clinically indicated for peripheral vascular disease. As used herein, the term atherosclerotic disease event " is intended to cover coronary heart disease events, cerebrovascular events, and intermittent claudication. People who have previously experienced one or more non-fatal atherosclerotic atherosclerotic disease events are 'thinking of the possibility of such events recurring. In addition, the invention also provides a method for preventing or reducing the risk of an atherosclerotic sclerosis event at the first or subsequent occurrence, which comprises administering to a patient at risk of such an event a prophylactically effective amount of a compound or composition of the invention. Patients may already have an atherosclerotic disease at the time of administration or may be at risk of developing the disease. Risk factors for the development of atherosclerotic disease events, including increasing age 85585 -109- 200307684 (65 years and over), male, family history of atherosclerotic disease events, high blood cholesterol (especially LDL or " "Bad" cholesterol (over 100 mg / gong), smoking and exposure to tobacco smoke, hypertension, diabetes, obesity, and physical inactivity. In another aspect, the method of the present invention is also used in patients with atherosclerotic diseases to remove cholesterol from tissue deposits such as atherosclerotic plaques or xanthomas, which is evidenced by clinical signs , Such as colic, trekking, noise, those who have suffered a myocardial infarction or transient hemorrhagic hair, or those diagnosed by vascular X-ray, sonic recording, or MRI. Methods to treat, prevent or ameliorate one or more symptoms of diabetes, and to treat complications of diabetes (see, for example, International Patent Application Publication WO 01/82917) are also provided using the compounds and compositions provided herein. Diabetes mellitus, commonly known as diabetes, refers to a disease or symptom that is generally characterized by metabolic defects in the production and use of glucose, which can result in failure to maintain proper blood glucose levels in the body (see, For example LeRoith, D. et al. (Eds.), Diabetes (Lippincott-Raven Press, Philadelphia, PA. USA 1996)). In the case of type 2 diabetes, the disease is characterized by insulin resistance, where insulin loses its ability to exert biological effects across a wide range of concentrations. This resistance to the insulin response results in insufficient insulin activation of glucose uptake, oxidation, and storage in muscle, as well as inadequate insulin repression of lipolysis in adipose tissue and glucose production and secretion in the liver (see, For example, Reaven G.M., J. Basic & Clin. Phys. &Amp; Pharm. (1998) 9: 387-406, and Flier, J. Ann Rev. Med. (1983) 34: 145-60) 85585- 110- 200307684. The cause of the symptoms is an increase in blood sugar, which is called, "hyperglycemia". Uncontrolled hyperglycemia is accompanied by increased and premature mortality, which is caused by an increased risk of microhemorrhagic and macrovascular diseases, including retinopathy (impaired or lost vision due to vascular injury in the eye) ; Neuropathy (neural injury and problems due to vascular injury to the nervous system); and kidney disease (renal disease due to vascular injury in the kidney), hypertension, cerebrovascular disease and coronary heart disease. Therefore, stability control such as glucose is an important way to treat diabetes. / Methods for treating, preventing, or improving insulin insensitivity or resistance—or multiple symptoms, and the complications of insensitivity or resistance to insulin (see, for example, International Patent Application Publication WOG1 / 82917), also Provided using the compounds and compositions provided herein. 'Treatment, prevention, or improvement of hyperglycemia—or multiple symptoms, and methods of treating concurrent hyperglycemia (see' e.g., International Patent Application Gazette Separate Section) are also provided using the compounds and compositions provided herein. Insulin resistance has been hypothesized to cause high blood pressure, glucose intolerance, blood isotrin, increased levels of triglyceride and reduced rib cholesterol, and CKS grouping obesity into one group. Insulin Resistance and Glucose: Prepared 〖Health% plus Plasma Triglycerides and Reduced HDL Cholesterol Degree: Blood Pressure, Hyperuricemia, Smaller, Dense Low Density Lipoprotein Granules2, and More Recycled% Content The junction of plasminogen activator inhibitor_1 has been identified as cluster X, (see, for example, Reaven GM ·, Physiol. Rev. (, 5) 75 · 47M86). Therefore, it provides a method for treating, preventing, or ameliorating any condition related to diarrhea, returning blood glucose, or insulin resistance, including a cluster of disease states, symptoms, or conditions that constitute " Sign 85585 • 111- 200307684 Hou Qiu x ". In addition, the present invention also provides a method for preventing or reducing the risk of hyperglycemia, insulin resistance or the development of diabetes in a patient, which comprises administering to a patient at risk of such an event a prophylactically effective amount of a compound of the present invention or The patient may already be obese (BMI 430.0 or greater), overweight to 30.0) or have other risk factors for developing diabetes, including age, family history, and physical inactivity.

Step C is provided herein by administering a compound or composition provided herein to treat, prevent or ameliorate one or more diseases of bile stagnation, and a method of treating complications of bile stagnation. Gallbladder / Shiyu is typically caused by alpha in one of the liver (intrahepatic) or extrahepatic (extrahepatic), and causes bile salts, bilirubin, and lipids to accumulate in the bloodstream. Instead of being removed under normal circumstances. ’

Intrahepatic bile stagnation is characterized by extensive obstruction of small ducts or some conditions, such as liver people, which can weaken the body's ability to remove bile. Intrahepatic bile stagnation also: due to alcoholic liver disease, primary biliary sclerosis, has been removed from another part of the body: Dao Zhengzheng (metastatic) <Rho, primary sclerosing cholangitis, gallstones, bile Caused by cholecystitis. It can also be caused by surgery, severe injury, gallbladder = infection or intravenous infusion or complications caused by drugs-: 'Shizhuo can also occur due to complications of pregnancy' and often under attack Development during the month. Liver = Juying stasis is most often caused by bile duct stone disease (biliary stone), benign and non-cancerous narrowing), bile duct cancer (ductal cancer), and cancer. Age stamps can occur due to the side effects of many medications. 85585 -112- 200307684 Q The compounds or compositions provided herein can be used to treat, prevent or improve one or more symptoms of intrahepatic or extrahepatic bile stagnation, including but not limited to cholestatic arteritis, obstetric bile stagnation , Neonatal bile stagnation, drug-induced &lt; bile stagnation, bile stagnation due to hepatitis C infection, chronic bile stagnation liver disease, such as primary biliary sclerosis (PBC) and primary sclerosing bile ducts Inflammation (PSC). The progress and donors of this month are methods for treating obesity and treating obesity complications by administering the compound or composition of the present invention. According to the World Health Organization, the term "obesity" refers to a body mass index (BMI) greater than 27.8 kg / m2 for men and 27.3 kg / m2 for women = (BMI is equal to body weight (kg) / height (square meters). Obesity is linked to a variety of medical symptoms, including diabetes and atherosclerotic sclerotic disease events (see, for example, B trace C0tr, E ·, EPidem0l · Rev · (1989) ll: 172-181; and Knowler et al., AmJ Clin · Nuir · (1991) S3: 1543-1551). Therefore, the claimed compound or composition can be used to treat obesity or its complications, and can be used as Identified, formulated, and administered as described above. Q. Combination therapy, also intended to be encompassed herein, is combination therapy, which uses—or more than one compound or composition provided herein or a pharmaceutically acceptable derivative thereof. 'And use one or more of the following: anti-hyperlipidemic agents, plasma disorder boosters, anti-hypercholesterolemia agents, cholesterol biosynthesis inhibitors (such as Thallium reductase inhibitors, such as lovastatin) 'Sinvastatin (_asta tin), pravastatin (tin), fuvastatin into tamarind, atovatatin (ato round tatin) and ristatin (-St-)), 醯 基 _ 助 85585 -113- 200307684 Enzyme A: Cholesterol hydrazone transferase (ACAT) inhibitor, probucol (prObuc01), raloxifene, nicotinic acid, nicotinamide, cholesterol absorption inhibition Agents, bile acid sequestrants (such as anion exchange resins or quaternary amines (such as cholestyramine or cholestyr)), low-density lipoprotein receptors Compounds, dofibrate, fenofibrate, benzofibrate, Cip0fibrate, gemfibrizol, vitamin β6, vitamin 2, Antioxidant vitamins, point-blockers, antidiabetic agents, angiotensin π antagonists, angiotensin converting enzyme inhibitors, platelet aggregation inhibitors, fibrinogen receptor antagonists, LXR α or / 5 Activators, antagonists or partial activators, aspirin or fibric acid derivatives. A compound or composition provided herein or a pharmaceutically acceptable derivative thereof is administered at the same time as or after the administration of one or more of the aforementioned agents. Also provided are pharmaceutical compositions comprising a compound I provided herein and one or more of the aforementioned agents. Combination therapy involves administering a single pharmaceutical dosage formulation containing a compound of the invention and one or more other active agents, and administering a compound of the invention and each active agent in its own individual pharmaceutical dosage formulation. For example, the farnesin XI body activator, partial activator, partial antagonist or antagonist, and hmg_Coa reductase inhibitor of the present invention can be used as single-oral dosage compositions, such as tablets or capsules. It is administered to the patient, or each medicament is formulated in a separate oral preparation. In the case of individual dosage formulations, the compounds described in the text and / or other active agents may be administered at substantially the same time, w P at the same time, or at the same time, which means that they are administered sequentially. It should be understood that combination therapy includes all such services. 4 85585 200307684 Examples of combination therapies that modulate or prevent the onset of atherosclerotic symptoms or associated complications, are administered with one or more of the following active agents: antihyperlipidemic agents; plasma HDL-raising agents; antihypercholesterol Anemia agents, such as cholesterol biosynthesis inhibitors, such as hydroxymethylglutaryl (HMG) CoA reductase inhibitors (also known as statins, such as lovastatin, simvastatin (Simvastatin), pravastatin, fluvastatin and atorvastatin), HMG-CoA synthetase inhibitor, squalene epoxidase inhibition Agents or synthetase inhibitors (also known as synthase inhibitors); amyl coenzyme A cholesterol and amyl transferase (ACAT) inhibitors, such as melinamide ); Probucol; nicotinic acid and its salts, and nicotinamide; cholesterol absorption inhibitors, such as / 3-sitosterol; bile acid sequestering anion exchange resins, such as cholestyramine ( cholestyramine), cholestyramine colestipol), or dialkylaminoalkyl derivatives of cross-linked dextran; LDL (low-density lipoprotein) receptor inducers; cellulosic acids, such as clofibrate, benzoheterocellate ( bezafibrate), fenofibrate, and gemfibrizol; vitamin B6 (also known as pyridoxine) and its pharmaceutically acceptable salts, such as HC1 salt; vitamin 坧 2 (also known as cyanide Cobalamine); Vitamin B3 (also known as nicotinic acid and nicotinamide, same as above); antioxidant vitamins, such as vitamins C and E and / 3 carotene; / 3-blockers; LXR α or / 3 Activators, antagonists or partial activators, angiotensin II antagonists; angiotensin-converting enzyme inhibitors; and platelet aggregation inhibitors, such as fibrinogen receptor antagonists (meaning glycoprotein Ilb / IIIa fibrinogen receptor antagonist) and aspirin. The compound or composition of the present invention is preferably administered together with a cholesterol biosynthesis inhibitor, 85585-115-200307684, especially a HMG-CoA reductase inhibitor. The term HMG-CoA reductase inhibitor is intended to include all pharmaceutically acceptable salt, ester, free acid, and lactone forms of a compound having HMG-CoA reductase inhibitory activity. Therefore, such salts, esters Uses of the form, free acid and lactone form are included within the scope of the present invention. Other HMG-CoA reductase inhibitors can easily be confirmed using tests known in the art. For example, appropriate tests are described or disclosed in U.S. Patents 4,231,938 and WO 84/02131. Examples of suitable HMG-CoA reductase inhibitors include, but are not limited to, lovastatin (MEVACOR®; see US Patent 4,231,938); simvastatin (ZOCOR®; see US patent 4,444,784); Pravastatin Sodium (PRAVACHOL®; see U.S. Patent 4,346,227); Fluvastatin Sodium (LESCOL®; See U.S. Patent 5,354,772); Atovastatin ) Calcium (LIPITOR®; see U.S. Patent 5,273,995) and rivastatin (also known as some cerivastatin); see U.S. Patent 5,177,080). The structural formulae of these and other HMG-CoA reductase inhibitors that can be used in the method of the present invention are described in M. Yalpani, &quot; Cholesterol-lowering drugs, π 必 # 和 工 裳, pp. 85-89 (1996 February 5) at page 87. In a specific embodiment, the HMG-CoA reductase inhibitor is selected from the group consisting of lovastatin and simvastatin. Dosage information for HMG-CoA reductase inhibitors is known in the art 'because several HMG-CoA reductase inhibitors are sold in the United States. In particular, the daily dose of the HMG-CoA reductase inhibitor can be the same or similar to the amount used for antihypercholesterolemia treatment, and is described in the shoulder of death 2 References (PHYSICIANS, DESK REFERENCE) (? OR). For example, participation 85585 -116-200307684 This 50th edition of the PDR, 1996 (Medical Economics Corporation); in particular, see page 216, titled M hypolipidemia ", subtitled" HMG-CoA reduction "Enzyme inhibitors", and the reference pages cited therein. The oral dose of the HMG-CoA reductase inhibitor is preferably about 1 to 200 mg / day, and more preferably about 5 to 160 mg / day. But The dosage will vary depending on the efficacy of the specific HMG-CoA reductase inhibitor used, as well as other factors as described above. HMG-CoA reductase inhibitors with sufficient efficacy can be given in sub-mg daily doses. Take the following As an example, the daily dose of simvastatin may be selected from 5 mg, 10 mg, 20 mg, 40 mg, 80 mg, and 160 mg, and 10 mg, 20 mg, 40 mg, and 80 mg; 20 mg, 40 mg, and 80 mg for vastatin sodium; and 10 mg, 20 mg, and 40 mg for pravastatin sodium. About daily administration of atovastatin The dose can be in the range of 1 mg to 160 mg, and more specifically, 5 G to 80 mg. Oral administration may be in single or divided doses of two, three or four times daily, but single daily doses of HMG-CoA reductase inhibitors are preferred. Most patients with diabetes will experience premature development. Incidence of atherosclerotic disease, and increased rates of heart and vascular and peripheral vascular disease. Hyperlipidemia and dyslipidemia are important precipitating factors for these diseases. See, for example, Wilson, J. et al. (Eds.) , Disorders of Lipid Metabolism, Chapter 23, Textbook of Endocrinology, 9th Edition (W_B. Sanders, Philadelphia, PA · USA 1998). Lipidemia disorders are characterized by abnormal levels of lipoproteins in the plasma (eg, increased Levels of LDL, VLDL, and reduced levels of HDL) and have been proven to be one of the major contributors to increasing the incidence of coronary events and deaths in diabetic patients (see, for example, Joslin, E. Ann. Chim · Med. · (1927) 5: 1061-1079). Since then 85585 -117- 200307684, epidemiological studies have confirmed its association and have been demonstrated in diabetic patients when compared to non-diabetic patients. Coronary deaths multiplied (see, eg, Garcia, MJ, et al., Diabetes (1974) 23: 105-11 (1974); and Laakso, M. and Lehto, S., Diabetes Review (1997) 5 (4): 294-315). The method of the present invention can be effectively combined with one or more other active antidiabetic agents, depending on the desired target therapy (see, for example, Turner, N. et al., Prog. Drug Res. (1998) 51 ··· 33-94; Haffher, S. Diabetes Care (1998) 21, 160-178; and DeFronzo, R. et al. (Eds.), Diabetes Review (1997) Vol. 5, No. 4). Many studies have explored the benefits of combination therapy with oral agents (see, eg, Mahler, R., J_ Clin. Endocrinol. Metab. (1999) 84: 1165-71; UK Prospective Diabetes Research Team: UKPDS 28, Diabetes Care (1998) 21: 87-92; Bardin, CW ·, (eds.), Current Therapies in Endocrinology and Metabolism, 6th Edition (Mosby—Almanac, St. Louis, Mo, 1997); Chiasson, J. et al., Ann · Intern. Med. (1994) 121 .. 928-935; Coniff, R. et al., Clin. Ther. (1997) 19: 16-26; Coniff, R. et al., Am. J. Med. (1995) 98: 443-451; and Iwamoto, Y. et al., 01 Wang 61:.] \ ^ (1 (1996) 13365-370; Kwiterovich, P. Am. J. Cardiol (1998) 82 (12A): 3U -17U). These studies show that the modulation of hyperlipidemia associated with diabetes can further improve the treatment outcome of diabetes. Therefore, another combination therapy requested herein is suitable for the treatment of diabetes and its related symptoms, complications, and Disorders, and includes co-administration of a compound or composition provided herein with, for example, peroxyurethanes (such as gas Urea, Tolbutamide, Cyclopenzamide, Mesosulfazone, Glyburide, Gliclazide, Glynase, Glimepiride (Gliniepiride) and glipizide), biguanides (such as metformin 85585 -118- 200307684 metformin), thiazolidinediones (such as dgiitazone, piogitta Pioglitazone, troglitazone, and rosiglitazone); and related insulin sensitizers, such as selective and non-selective activators of PPARa, PPAR / 3, and PPARr; LXRa or / 3 activator, antagonist and partial activator, dehydroepiandrosterone (also known as DHEA or its conjugate sulfate DHEA-S04); anticorticoid; TNFα-inhibitor; α- Glucosidase inhibitors (such as acarbose, miglitol and voglibose), pramlintide (synthetic analogue of human hormone dextrin), others Insulin secretagogues (such as repaglinide, gliquidone, and nateglinide )), Insulin, and the active agents discussed above for the treatment of atherosclerosis. Another example of a combination therapy requested herein is a co-administration of a requested compound or composition provided herein with a compound or composition for treating obesity or an obesity-related disorder, wherein the requested compound is effective For example, phenylpropanolamine, phentermine, diethylamine phenone, and phentermine Θ; fenfluramine, dexfenfluramine, and phentilamine ( phentiramine), Lu 3 adrenergic receptor activators; sibutramine, gastrointestinal lipase inhibitors (such as orlistat), LXR α or no activator, antagonist and part Activators, and Leptone. Other agents used in the treatment of obesity or obesity-related disorders, including neuropeptides, enterostatin, cholangiatin, bombesin, dextrin, histamine H3 receptors, dopamine D2 receptors, Melanocyte hormone, corticotropin releasing factor, galangin and 7 aminobutyric acid (GABA). Another example of a requested combination therapy is co-administration of the 85585 -119- 200307684 requested compound or composition provided herein with a compound or combination for the treatment of bile stagnation and its related signs, complications and conditions Thing. Such co-administered compounds include, for example, Actigall (Usodeoxycholic Acid-UDCA), corticosteroids, anti-infectious agents (Rifampin, Rifadin, pjmactane), antivirals, vitamin D, vitamin A, One of phenobarbital, cholestyramine, UV light, antihistamines, oral opioid receptor antagonists and bisphosphates for the treatment, prevention or improvement of intrahepatic or extrahepatic bile stagnation Or multiple symptoms. The dosage information for these agents is known in the art. [Embodiments] The following examples are provided for illustrative purposes only and are not intended to limit the scope of the invention. Example 1 Preparation of 1,2,3,6-tetrahydronitrogeno [4,5-B] ^ indole-5-acrylic acid ethyl ester

A. A mixture of tryptamine hydrochloride (1.96 g, 10 mmol), ethyl 3-bromopyruvate (1.67 ml, L2 equivalent), and decolorized carbon (0.5 g) in absolute ethanol was Heat to reflux overnight under nitrogen. TEA was added and the reaction mixture was heated to reflux for another 7.5 hours. After cooling, the carbon was removed by filtration and washed with ethanol. The filtrate was concentrated under vacuum and diluted with water (20 ml). Then, it was extracted with EtOAc (3x30 mL), and the combined organic layers were washed with brine and dried over MgS04. The solvent was evaporated and recrystallized from DCW hexane to obtain the title compound (U7 g). iH-NMRCCDClJ ·· δ 85585 -120- 200307684 10.49 (1H, br s), 7_79 (1H, d), 7.43 (1H, d), 7.43 (1H, d), 7.06 (2H, m) , 5.27 (1H, br s), 4.29 (2H, q) 3.58 (2H, m), 3.17 (2H, m), 1.36 (3H, t); MS (ES): 257 (MH +). B. Similar Method, but replacing tryptamine hydrochloride with appropriately substituted tryptamine to prepare the following compounds: 9-methoxy-1,2,3,6-tetrahydronitrogeno [4,5-b] pyridine- 5-carboxylic acid ethyl ester; 1H-NMR (CDC13): δ 10.36 (1H5 br s) 5 7.80 (1H5 d)? 7.21 (1H5 d) 5 6.87 (1H? D)? 6.75 (1H5 dd), 5.28 (1H , Br s), 4.27 (2H, q), 3.86 (3H, s), 3.62 (2H, m), 3.14 (2H, t), 1.34 (3H, t); MS (ES): 287 (MH +); 8-methoxy-l, 2,3,6-tetrahydronitrogen is eh [4,5-b] e indole-5-carboxylic acid ethyl ester; 9-fluoro-1,2,3 , 6-Tetrahydronitrogero [4,5Seven &gt; 5 丨 Indole-5-carboxylic acid ethyl ester; 1HNMR (CDC13): δ 10 · 50 (1H, br s), 7.82 (1H, d), 7.20 (1H, dd), 7.03 (1H, dd), 6.81 (1H, m), 5.30 (1H, br s), 4.27 (2H, q), 3_61 (2H, m), 3.11 (2H, t) , 1.34 (3H, t); MS (ES): 275 (MH +); 9-chloro-1,2,3,6-tetra Nitrogen [4,5 hept] ardol-5-carboxylic acid ethyl ester; 1H-NMR (CDCI3): δ 10.56 (1H, br s), 7.82 (1H5 d) 5 7.35 (1H5 d) 5 7.21 (1H5 d) 5 7.14 (1H, dd), 5.34 (1H, br s), 4.26 (2H, q), 3.58 (2H, m), 3.10 (2H, m), 1.34 (1H, t ); MS (ES): 290 (MH +); 8-fluoro-1,2,3,6-tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid ethyl ester; 1H-NMR (CDCI3): (5 10.51 (1H, br s), 7.79 (1H, d), 7.28 (1H, dd), 6.99 (1H, dd), 6.80 (1H, m), 4.27 (2H, q), 3.59 (2H, m), 3.14 (2H, m), 1.34 (1H, t); MS, (ES): 274 (MH +); 7-methyl-1, 2, 3, 6-tetrahydro Nitrogen [4,5-bH-indol-5-carboxylic acid ethyl ester; 1H-NMR (CDCI3): (5 10.43 (lH, brs), 7.82 (lH, d), 7.27 (lH, m), 6.98 (lH, m), 6.89 85585 -121-200307684 (1H, d), 5.29 (1H, br s), 4.27 (2H, q), 3.61 (2H, m), 3.17 ( 2H, t), 2_51 (3H, s), 1.36 (3H51); MS (ES): 271 (MH +); 9_hydroxy-1,2,3,6-tetrahydronitrogen is hydride [4,5-b ] Pyridine-5-carboxylic acid ethyl ester; MS (ES): 273 (MH +); 9-bromo-1,2,3,6-tetrahydronitrogeno [4,5-b] pyridine-5 _Ethyl carboxylate 1H-NMR (CDC13): 510.37 (1H, s), 7.62 (1H, d), 7.31 (1H, d), 6.96 (2H, m) 5 5.13 (1H, s), 4.17 (2H, dd), 3.38 (2H, m ), 2.90 (2H, m), U3 (3H, t); MS (ESI): 335, 337 (MH +); 7-fluoro-1, 2, 3, 6-tetrahydronitrogen is entrained [4,5 -b] ethyl indole-5-carboxylic acid; MS (ES): 275 _ +); 7-fluorenyl1,2,3,6-tetrahydronitrogeno [4,5 七] 4 丨 indole -5-Ethyl Acetate; and 10-Ethyloxy-1,2,3,6-tetrahydronitrile [4,5 七] # 丨 Homo-5 · Ethyl Acetate and 4-Methoxy Amine hydrochloride. Example 2 Preparation of 3- (4-fluorobenzyl) 1,2,3,6-tetrahydroazepine [4,5_: 8], 5 丨 indole · 5-acrylic acid ethyl ester

A. In a solution of U, 3,6-tetrahydronitrocarba [4,5seven] indole-5_carboxylic acid ethyl ester (Example i, 52 Φ g, 0.2 mmol) in DCM, add Chlorinated 4-benzyl donkey (36 µl '0.2¾ mole) and Alkali (56 µl, 0.4 mmol) were allowed to stand and the mixture was shaken overnight under a thief. Add tromethamine resin (mg mg), and shake the suspension 85585 -122- 200307684 at 20 ° C for 2 hours. Pass the florisil cartridge and remove the resin by filtration. The solvent was evaporated to obtain a crude product, which was purified by trituration with methanol to obtain the title compound (28 mg); 1H-NMR (CDC13): δ 10.31 (1H, br s), 7.79 (1H, s), 7.41 (2H, m), 7.36 (1H, d), 6.90-7.04 (5H, m), 3.99-4 · 06 (4H, m) 5 3.06 (2H, t), 1.02 (3H, t); MS (ES): 379 (MH +) ·

B. In a manner similar to that described in step A, but using appropriately substituted 1,2,3,6-tetrahydronitrogen in the example iB, [4,5Hepta] indole-5-carboxylic acid ethyl ester , The following compounds were prepared: I 9-hydroxy-l, 2,3,6_tetrahydronitrogeno [4,5_b] pyrene-5-carboxylic acid ethyl ester. 1H-NMR (CDC13): δ 10.57 (1H5 s), 8.26 (1H? M) 5 7.83 (1¾ d) 5 7.32-7.16 (5H5 m) 5 6.88 (lH, d), 5.35 (lH, s) 54.28 ( 2H, q), 3.62 (2H, m), 3-14 (2H, m), 1.35 (3H, t). MS (ES): 395 (MH +); 7-fluoro-3- (4-fluorobenzidine Yl) -1,2,3,6-tetrahydronitrogeno [4,5 hepta] oxindole-5-carboxylic acid ethyl ester; MS (ES): 397 (MH +); 7-benzyloxy-3- (4-fluorobenzylidene) -1,2,3,6-tetrahydronitrocarbazone [4,5hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 485 (MH +); and Lu 10-benzyloxy-3- (4-fluorobenzylidene) -1,2,3,6-tetrahydronitrocarba [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES): 485 (MH +). C_ is similar to step 骡 A, but uses 10-benzyloxy · 1,2,3,6-tetrahydronitrogen to indole [4,5 七] indole-5- Ethyl carboxylate, replacing 1,2,3,6-tetrahydronitrogen with [4,5_b] ^ indole-5-carboxylic acid ethyl ester, and replacing 3,4-difluorobenzidine chloride with chloro 4-Fluorobenzylpyridine to prepare the following compounds: 10-benzyloxy each (3,4-difluorobenzyl) -1,2,3,6-tetrahydroazepine [4,5VII; ^丨 Ethyl indole-5-carboxylic acid; MS (ES) ·· 503 (MH +) · 85585 -123- 200307684 D · In a manner similar to Step A, but using 5,6,7, 12-tetrahydrobenzo [2,3] nitrogeno [4,5-b] indole, replacing 1,2,3,6-tetrahydronitrogeno [4,5hepta] pyridin-5-carboxy Acid ethyl ester to prepare the following compounds: (6,7-dihydro · 12Η-benzop, 3] nitrogeno [4,5-13] pyridin-5-yl)-(4-fluorophenyl)- Methyl ketone, 5,6,7,12-tetrahydrobenzo [2,3] nitrogen [4,5-b] radol 1H-NMR (CDC13): 5 8 · 31 (1H, s), 7.70 (H, d), 7.61 (1H, d), 7.44 (1H, d), 7.25-7.32 (2H, m), 7.18 (1H, m), 7.10 (2H, m) , 6.99 (1H, m), 6.99 (1H, m), 6.76 (3H, dd), 5.28 (1H, m), 3.63 (1H, m), 3.20 (2H, m) · MS (ES): 437 (MH +) · E · In a manner similar to that described in step 骡 A, but using appropriately substituted fluorene chloride, chloroformate, or isocyanate, in place of 4-fluorobenzoyl chloride , The following compounds were prepared: 3- (4-p-methoxybenzyl) -1,2,3,6_tetrahydronitrogeno [4,5-bH 丨 indole-5-carboxylic acid ethyl ester; 1H- NMR (CDC13): (5 10.46 (lH, brs), 8.04 (1H, s) 5 7.45 (lH, d), 7.30 (2H, m), 7.13 (1H, m), 6.98-7 · 06 (4H, m), 4.12-4.18 (4H, m), 3.78 (3H), s) 3.20 (2H, m), U5 (3H, t); MS (ES): 779 (MH +) ; 3- (4-chlorobenzylidene) -l, 2,3,6-tetrahydronitropyro [4,5 hepta] indole-5-carboxylic acid ethyl ester; iH-NMRCCDClJ: 6 10.34 ( lH, brs), 7.81 (lH, s), 7.34-7.37 (3H, m), 7.27-7.29 (2H, m), 7.20 (1H, d), 7.05 (1H, m), 6.94 (1H, m) , 4 · 09 (2H, q), 4 · 08 (2H, t), 3.09 (2H, t), 1.02 (3H, t); MS (ES) ·· 395 (MH +); 3- (2,4 -Dichlorobenzylidene) -1,2,3,6-tetrahydronitrogeno- [4,5-b] indole-5 · carboxylic acid ethyl ester; 1 H-NMR (CDC13): (5 10.55 (1H, br s), 7.60 (2H, m), 7_42-7 · 48 (3H, m), 7.23 (1H, m) 5 7.01-7.08 (1H, m), 6.94 (1H, m) 5 4 · 30 (4H, m), 3.34 (2H, m), 1.35 (3H, m) MS (ES) · 429 (MH +); 3-benzylidene-1, 2, 3, 6 -Tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid ethyl ester; 1H- 85585 -124- 200307684 NMR (CDC13) ·· (5 10.46 (1H, br s), 8.01 (1H, s) 5 7.50 (2H, m), 7.46 (2H, m), 7.42 (2H, m) 5 7.34 (1H, m), 7.14 (1H, m), 7.05 (1H, m), 4.19-4 · 33 (4H, m), 3.22 (2H, t), 1.13 (3H, t); MS (ES): 361 (MH +); 3- (2,4-difluorobenzene Formamyl) -l, 2,3,6_tetrahydronitrogeno- [4,5-b] Indole 5-carboxylic acid ethyl ester; 1 H-NMR (CDC13): 510.49 (1H, br s), 7.79 (1H, s), 7.50 (2H, m), 7.37 (1H, d ), 7.19 (1H, m), 7.10 (1H, m), 7.02 (1H, m), 6.93 (1H, m), 4.25 (2H, q), 4.16 (2H, m ), 3.24 (2H, t) 5 1.25 (3H, t); MS (ES): 397 (MH +); 3-nicotinofluorenyl-1,2,3,6-tetrahydronitrogen is [4 , 5-bHI indole-5-carboxylic acid ethyl ester; 1 !!-NMR (CDC13): 5 10 · 46 (1H, br s), 8.80 (2H, m), 7.97 (1H, br s ), 7.91 (1H, m), 7.51 (1H, d), 7_42 (2H, m), 7.22 (1H, m), 7.12 (1H, m), 4.25 (4H, m), 3. · 29 (2H, m), 1.22 (3H, t); MS (ES): 362 (MH +); 3- (2-Methylmethyl) -l, 2,3,6-tetrahydronitrogen [4,5-b] Indole-5-carboxylic acid ethyl ester; 1H-NMR (CDC13): (5 10.48 (lH, brs), 8.14 (lH, s), 7.66 (4H, m), 7.54 (lH , D), 7.48 (2H, m), 7.39 (2H, m) 5 7.20 (1H, m), 7.11 (1H, m), 4.23 (4H, m), 3.30 (2H , m), 1.21 (3H, t); MS (ES): 411 (MH +); 3- (3-tolylmethyl) -l, 2,3,6-tetracarbazine [4, 5-b] oxindole-5-carboxylic acid ethyl ester; 1 H-NMR (CDC13): (5 10.53 (lH, brs)? 8.11 (1H5s) 5 7.52 (lH? d) 5 7.37 (5H5m) 5 7.20 (1H, m), 7.11 (1H, m), 4_22 (4H, m), 3.26 (2H, m), 2.41 (3H, s), 1.21 ( 3H, t); MS (ES): 375 (MH +); 3- [2,5-bis (trifluoromethyl)] benzylidene) -l, 2,3,6-tetrahydronitrogen [ 4,5-b] W 丨 Indole-5-carboxylic acid ethyl ester; 1 H-NMR (CDC13) ·· Rotomers (3: 7) (5 10.58 (0.3H, br s), 10.41 (0.7H , S), 8.67 (0.3H, br s) 7.93 (2H, m), 7.55 (1H, d), 7.50 (0 · 7Η, s), 7.34 (1 · 3Η , M), 7.22 (1 · 7Η, m), 7 · 12 (1Η, m), 4.0 · 4 · 40 (3.4Η, m), 3.85 (0 · 3Η, m), 3.69 (0 · 3Η, m), 3.29 (1 · 4Η, m), 2.99_3 · 18 (0 · 6Η, m), 1.43 (0 · 9Η, m), 1.06 85585 -125- 200307684 (2 · 1Η, t); MS (ES) ·· 497 (MH +); 3- (4-methoxyphenoxycarbonyl) -l, 2,3,6-tetrahydronitrogen [4, 5-b; H, indole-5-carboxylic acid ethyl ester; 1H-NMR (CDC13): δ 10.51 (1H, br s), 8.37 (1H, s), 7.45 (1H, m) 5 7 20 (5H, m), 6.86 (2H, m), 4.31 (2H, m), 4.08 (2H, m), 3.76 (3 H, br s), 3.20 (2H, m), 1 32 (3H, m); MS (ES): 407 (MH +); 3- (2,4-dichlorobenzene Carboxymethyl) -1,2,3,6-tetrahydronitrocarbazone [4,5-b; E-indol-5-carboxylic acid ethyl ester; 1 H-NMR (CDC13): 5 10.51 (1H, br s), 8.15 (1H, d), 8.10 (1H, s), 7.46 (1Η, d), 7.12-7.35 (4Η, m) 7.04 (1Η, m), 4.33 ( 2Η, q), 4 · 04 (2Η, t), 3 · 18 (2H, t) 5 1 · 34 (3H, t); MS (ES): 444 (MH +); 3- (4_ethylbenzene (Methylmethyl) · 1,2,3,6-tetrahydronitrocarbazone [4,5Hepta] indole-5 · Ethyl Carboxylate; MS (ESI): 393 (MH +); 3- (Pyrimidine- 2-carbonyl) -l, 2,3,6-tetrahydronitrogeno [4,5-b] oxindole-5-carboxylic acid ethyl ester; MS (ES): 367 (MH +); 3-cyclohexylcarbonyl -1,2,3,6-tetrahydronitrocarbazone [4,5Hepta] indole-5-carboxylic acid ethyl ester]] ^ 3): 367 (MH +); 3- [3- (2-chloro -6-fluorophenyl) · 5-methylisoxazole-4-carbonyl] -1,2,3,6-tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid ethyl Esters; MS (ES) ·· 494 (MH +); 3- (Benzo [b &gt; Sphene_2_fluorenyl) -l, 2,3,6-tetrahydronitrogen [4,5-b] W 丨 Homo-5-carboxylic acid ethyl ester; MS (ES): 417 (MH +); 3-Phenethylfluorenyl-1,2,3,6-tetrahydronitrogeno [4,5_b] indole-5 -Ethyl methanoate; MS (ES): 375 (MH +); 3- (3-methoxybenzylhydrazyl μ, 2,3,6-tetrahydronitropyrene [4, 5-b] ethyl indole-5-carboxylic acid; MS (ES): 391 (MH +); 1,6-dihydro_2H-nitrogeno [4,5-b; HI indole-3,5- 5-ethyl 3-phenyl dicarboxylate; MS (ES) 85585 -126- 200307684: 377 (MH +); 1,6-dihydro-2H-nitrogeno [4,5-b] indole_3 3,4-dicarboxylic acid 3- (4-chlorophenyl) ester 5. Ethyl MS (ES): 411 (ΜΗ +); 1,6-dihydro-2H-nitrogeno [4,5-b] Indole-3,5-dicarboxylic acid 5-ethyl 3-p-tolyl ester; MS (ES): 391 (MH +); 3-anilinemethyl-1,2,3,6-tetraargonium Benz [4,5Hepta] oxindole-5-carboxylic acid ethyl ester MS (ES) ·· 376 (MH +); 3- (4-chlorophenylaminemethyl) 1,2,3,6-tetrahydro Azapine [4,5-b] i 丨 Homo-5-acrylic acid ethyl ester; MS (ES): 410 (MH +); 3- (4-methoxyphenylamine formamidine) -1,2, 3,6-tetrahydrozine benzo [4,5 hepta] oxindole-5-carboxylic acid ethyl ester; MS (ES): 406 (MH +) 3-p-tolylaminomethylamido-1,2,3 , 6-Tetrahydronitrogeno [4,5-b] &lt; Ethyl indole-5-carboxylic acid; MS (ES): 390 (MH +); 3-Ethyl-1,2,3,6_ Tetrahydronitro appeals to [4,5 hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 299 (MH +); 3- (2,3-difluorobenzyl) -1,2, 3,6-Tetrahydronitrogeno [4,5Hepta] indole-5 · carboxylic acid ethyl ester; MS (ES): 397 (ΜΗ +); 3- (2,5-difluorobenzidine ) 1,2,3,6_tetrahydronitrogeno [4,5Hepta] oxindole-5-carboxylic acid ethyl ester; MS (ES): 397 (ΜΗ +); 3- (2,6-di Fluorobenzyl) -1,2,3,6-tetrahydronitrocarba [4,5Hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 397 (MH +); 3_ (3, 4_difluorobenzyl))-1,2,3,6_tetrahydronitrocarba [4,5Hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 397 (MH +); 3 -(3,5-difluorobenzylidene) -1,2,3,6_tetrahydroazepine [4,5Hepta] pyrene-5-carboxylic acid ethyl 85585 -127- 200307684 ester; MS ( ES): 397 (MH +); 3- (2,3,4_trifluorobenzyl) _1,2,3,6_tetrahydronitrogeno [4,5-b] indole-5-carboxy Ethyl Ester; MS (ES): 415 (MH +); 3- (2,3,6_trifluorobenzylidene) -l, 2,3,6-tetrahydronitrogen [4,5-b ] Indole-5_carboxylic acid ethyl ester; MS (ES) ·· 415 (MH +); 3_ (2,4,5_trifluorobenzylidene) · 1,2,3,6-tetrahydroazepine Benzo [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES): 415 (MH +); 3- (2,3,4,5-tetrafluorobenzyl) 1,2, 3,6_tetrahydronitropyridine [4,5Hepta] oxindole-5-carboxylic acid ethyl ester; MS (ES): 433 (MH +); 3-pentafluorobenzyl-1,2,3, 6-tetrahydronitrogeno [4,5-order 5 丨 indole-5-carboxylic acid ethyl ester; MS (ES): 451 (MH +); 3- (3,5_bis-trifluoromethylbenzidine Base) -1 2,3,6-Tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES): 497 (MH +); 3- (2-fluorobenzyl) 1 , 2,3,6-Tetrahydronitrogen benzo [4,5Hepta] oldole-5-carboxylic acid ethyl ester; MS (ES): 379 (MH +); 3- (3-fluorobenzyl)- l, 2,3,6-tetrahydronitrogen benzo [4,5-imide? indol-5-carboxylic acid ethyl ester; MS (ES): 379 (MH +); 3- (2-trifluoromethylbenzene (Methylamidino) -l, 2,3,6-tetrahydronitrocarbazone [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES): 429 (MH +); 3- (3 • Trifluoromethylbenzyl))-1,2,3,6-tetrahydronitrogeno [4,5-b &gt;? 丨 Indole-5-carboxylic acid ethyl ester; MS (ES): 429 (MH +) ; 3- (4-trifluoromethylbenzylidene) -1,2,3,6-tetrahydronitrocarbazone [4,5hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 429 (MH +); 3- (pyridine-4 · fluorenyl) -1,2,3,6-tetrahydronitrocarba [4,5 hepta] oxindole-5-carboxylic acid ethyl ester; 85585 -128- 200307684 MS (ES): 362 (MH +); 3- (4-cyanobenzyl) -l, 2,3,6-tetrahydronitrile [4,5-b] indole-5-carboxylic acid Ethyl ester; MS (ES): 386 (MH +); 3- (4-nitrobenzylidene) -i, 2,3,6-tetrahydroazepine [4,5-b; Ndole-5 -Ethyl carboxylate; MS (ES): 406 (MH +); 3- (4-methyl-3-nitrobenzylidene) -1,2,3,6- Hydrogen and nitrogen enzymatic [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES): 420 (MH +); 3_ (3,4_dimethoxybenzyl) -1,2, 3,6-Tetrahydronitrogeno [4,5_b] indole-5-carboxylic acid ethyl ester; MS (ES): 421 (MH +); 3- (2-methylbenzyl) -1,2 , 3,6-tetrahydronitropyre [4,5 七] # 丨 OLED_5_carboxylic acid ethyl ester; MS (ES): 375 (MH +); 3- (4-methylbenzyl)- l, 2,3,6-tetrahydronitrogen benzo [4,5-b] indole · 5-carboxylic acid ethyl ester; MS (ES): 375 (MH +); 3- (2-aminobenzidine Radical) -l, 2,3,6-tetrahydronitrogen benzo [4,5-b: ethyl ndol-5-carboxylic acid; MS (ES): 395 (MH +); 3- (4-methoxy Carbonyl benzamidine) -1,2,3,6-tetrahydronitrogeno [4,5 hepta] indolecarboxylic acid ethyl ester; MS (ES) ·· 419 (MH +); 3 · (biphenyl _4_carbonyl) -l, 2,3,6-tetrahydronitrocarbazone [4,5Hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 437 (MH +); 3- (3- Chlorobenzyl))-1,2,3,6-tetrahydronitrocarba [4,5-b; ethyl ester of indole-5-carboxylic acid; MS (ES): 395 (MH +); and 3- (4-Fluorosulfofluorenyl-benzylidene) -1,2,3,6-tetrahydronitrogeno [4,5H &gt;? 丨 Indole-5-carboxylic acid ethyl ester; MS ( ES): 443 (MH +). Example 3 85585 -129- 200307684 3,2,3,6-Four wind nitrogen entrains [4,5 _B] ^ 1 嗓 -5_ Preparation of isopropyl isopropanol

N A-Oi-Pr Η 6 A · Place 3-bromopyruvic acid · hydrate (3.34 g, 20 mmol) in a flask, and add U-digasmethylmethyl at 20 ° C Ether (3.7 ml, 20 mmol). The mixture was heated to 5 ° C. and stirred, and within 10 minutes, a clear solution was obtained. Heating was continued for 2 hours. The solvent was removed under high vacuum to give 3-bromoacetone chloride (6 g, 90 % Pure by IjjnMR), this compound was used without further purification. B. At -5 ° C in isopropanol, 3-bromoacetone chloride (5 g) was added dropwise and the solution was added. Stir overnight at 20 ° C. Evaporate the solvent to obtain isopropyl 3-bromopyruvate (3.5 g) and use it in the next step without further purification. C. The title compound is similar to that in Example 1A The method described above is made using isopropyl 3-bromopyruvate in isopropanol; iHNMR (DMSO): 510.61 (1H, br s), 7.81 (1H, s) 5 7 · 67 (1H , M), 7.28 (2H, m), 6_83 (1H, m), 4.96 (1H, br s), 3.39 (2H, m), 3.27 (1H, m), 2.93 ( 2H, m), 1.20 (6H, d); MS (ES): 2Ή (MH +). Example 4 &gt; Benzylidene 1,2,3,6-tetrahydronitrogen [4,5 -B] Preparation of indole-5 · isopropyl carboxylate

85585 -130- 200307684 Α · The title compound was used in a manner similar to that described in Example 2A to utilize 1,2,3,6-tetrahydronitrogen to inactivate [4,5 hepta] indole-5-carboxylic acid isopropyl ester. (Example 3) Made with benzamidine chloride; 1 H-NMR (CDC13): (5 10.48 (1H, br s), 7.98 (1H, s), 7.47 (2H, m), 7.41 (2H5 m), 7.40 (2H, m), 7.30 (1H, m), 7.15 (1H, m) 5 6.99 (1H, m), 5.04 (1H, m), 4.15 ( 2H, t), 3.2 (2H, d) 5 U0 (6H, d); MS (ES): 375 (MH +). B. In a similar manner, but using appropriately substituted thorium chloride and chloroformic acid Esters, isocyanates or sulfonium chloride, replacing benzamidine chloride, to prepare the following compounds: 3- (4-fluorobenzyl) -1,2,3,6-tetrahydronitrogen [4,5 -b] indole-5-carboxylic acid isopropyl ester; 1 H-NMR (CDC13): 510.43 (1H, br s), 7.86 (1H, s), 7.50 (2H, m), 7_41 (1H, d)), 7.26 (1H, d), 6.98-7.15 (4H, m), 5.02 (1H, m), 4.10 (2H, t), 3.2 (2H, d), 1.09 (6H , M); MS (ES): 393 (MH +); 3- (4-p-methoxybenzylidene) -l, 2,3,6_tetrahydronitrogen [4,5-b; N indole -5_ isopropyl carboxylic acid; iH-NMRCCDC ^) · 5 10_45 (lH brs), 8.27 (lH, s), 7.47 (lH, d), 7.22 (1H, d), 7.03 (1H, m), 6.90 (4H, m), 6.77 (2H, m), 5.07 (1H, m), 3.99 (2¾ m), 3.11 (2H, d), 1.21 (6H, d); MS (ES): 421 (MH +); # 3-Sunflower fluorenyl-1, 2 , 3,6-Tetrahydronitrogeno [4,5Hepta] indole-5-carboxylic acid isopropyl ester; iH-NMRCCDC ^): 5 10.52 (lH, brs), 8.04 (lH, s), 7.48 ( lH, d), 7.33 (1H, d), 7.15 (1H, m), 7.08 (3H, m), 6.82 (1H, 8.5), 6.02 (2H, s), 5. 17 (1H, m), 4.17 (2H, d), 3.11 (2H, d), 1.20 (6H, d); MS (ES): 419.2 (MH +); 3-phenoxycarbonyl -1,2,3,6-tetrahydronitrocarbazone [4,5-b] indole-5-carboxylic acid isopropyl ester; 1 H-NMR (CDC13): 5 10.47 (1H, br s), 8_29 (1H, s), 7.38 (1H, d), 7_23-7 · 31 (3H, m), 7.16 (1H, d), 7.06 (3H, m), 6.97 (1H, m), 5.10 (1H , M), 4.02 (2H, m), 3.13 (2H, d), 1.24 (6H, d); MS (ES): 391 (MH +); 85585 -131- 200307684 3- (2,4-dichlorobenzene Methylaminomethyl) -1,2,3,6-tetrahydronitrocarba [4,5Hepta] 4 丨 isopropyl-5-carboxylic acid isopropyl ester; 1 H-NMR (CDC13): accounting for 10.41 (1H , Br s), 8.06 (1H, d) 7.92 (1H, s), 7.31 (1H, d), 7.07-7.21 (4H, m), 6.90 (1H, m), 6.97 (1H, m), 5.07 (1H, m), 3.89 (2H, t), 3.04 (2H, t) 5 1 · 18 (6H, d); MS (ES): 458 (MH +); 3- (4-tert-butylbenzenesulfonyl) -l, 2,3,6-tetrahydronitropyrene [4,5-b; N-dodecyl-5-carboxylic acid isopropyl ester; 1 H-NMR (CDC13): 5 10.52 (1H, br s), 8.43 (1H, d), 7.79 (2H, d), 7.56 (2H, d), 7.40 (1H, d), 7.33 (1H, d), 7.15 (1H, m), 7.05 (1H, m), 5.23 (1H, m), 3.84 (2H, t), 3.00 (2H, t), 1.41 (6H, d) 5 1.33 (9H, s); MS (ES): 467 ( MH +); 3- (4-chlorobenzylidene) -l, 2,3,6-tetrahydronitrogeno [4,5-1)] pyridin-5-carboxylic acid isopropyl ester; MS ( ES): 409 (MH +) 3-Anilinomethyl-1,2,3,6-tetrahydronitrocarba [4,5Hepta] indole-5-carboxylic acid isopropyl ester; MS (ES): 390 (MH +); 3- (4-chlorophenylaminocarbamate) -l, 2,3,6-tetrahydronitrogen denote [4,5-b] 4 丨 Homo-5-carboxylic acid isopropyl ; MS (ES): 424 (MH +); 3-p-Tolyl carbamate-1,2,3,6-tetrahydronitrocarba [4,5-b] 4 丨 Homo-5-carboxylic acid iso Propyl ester; MS (ES): 404 (MH +); 3-phenylethylfluorenyl-1,2,3,6-tetrahydronitrogen [ 4,5-b] W 丨 Hou · 5 · Isopropanoic acid; MS (ES): 389 (MH +); 3- (4-methoxybenzyl) -l, 2,3,6- Tetrahydronitrogeno [4,5-b] indone-5_carboxylic acid isopropyl ester; MS (ES): 405 (MH +); 1,6-dihydro-2H-nitrogeno [4,5 七] Zhaodole-3,5-dicarboxylic acid 3- (4-chlorophenyl) ester 5-isopropyl ester; MS (ES): 425 (MH +); 1,6-dihydro-2H-nitrogen [ 4,5-b] indole-3,5-dicarboxylic acid 5-isopropyl ester 3-p-toluene 85585 132- 200307684 ester MS (ES): 405 (MH +); 3- (4-methoxyphenyl Carboxymethyl) 1,2,3,6-tetrahydronitrocarbazone [4,5-b] indole-5-carboxylic acid isopropyl ester; MS (ES) ·· 420 (MH +); 3-non Acid group 1,2,3,6_tetrahydronitrogen, and [4,5-b] indeno-5_isopropyl isopropyl ester; MS (ES): 411 (MH +); 3_ (2-methoxy Benzamidine) -1,2,3,6_tetrahydronitrogeno [4,5hepta] indole-5_carboxylic acid isopropyl ester; MS (ES): 405 (MH +); 3- (3 -Phenylpropionyl) -1,2,3,6-tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid isopropyl ester; MS (ES): 403 (MH +); 3 -(Toluenesulfonyl) _i, 2,3,6-tetrahydronitrogeno [4,5 hepta] indole-5-carboxylic acid isopropyl ester; MS (ES): 425 (MH +); 3- (4-Chlorobenzenesulfonyl) -1,2,3,6-tetrahydronitrocarbazine [4,5Hepta] pyrene-5-carboxylic acid Propyl ester; MS (ES): 445 (MH +); 3- (4-methoxybenzenesulfonyl) -l, 2,3,6-tetrahydronitrogen [4,5hepta] pyridin-5 -Isopropyl carboxylic acid; MS (ES): 441 (MH +); 3- (3,4-dimethoxybenzenesulfonyl) -1,2,3,6-tetrahydronitrogen [4, 5-b] isopropyl-5-carboxylic acid isopropyl ester; MS (ES): 471 (MH +); 3- (4-trifluoromethoxybenzenesulfonyl) -1,2,3,6-tetrakis Hydrogen and nitrogen enzymatic [4,5 hepta] indole-5 · isopropyl carboxylate; MS (ES): 495 (MH +); 3_ (2,4-dichlorobenzyl) -1,2,3 , 6-Tetrahydronitrobenzyl [4,5Hepta] indole-5-carboxylic acid isopropyl ester; MS (ES): 443 (MH +); 3- (3-methoxybenzyl) -1, 2,3,6-Tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid isopropyl ester; MS (ES): 405 (MH +); and M benzo [1,3] dioxo Woodinene-5-carbonyl) -1,2,3,6-tetrahydronitrocarba [4,5-b] indole- 85585 -133- 200307684 5-carboxylic acid isopropyl ester; MS (ES): 419 (MH +) · Example 5 Preparation of 3-benzylhydratino-1,2,3,6-tetrahydronitrogeno [4,5_BH 丨 indole-5-carboxylic acid n-propyl ester

A. In a manner similar to that described in Example 1A, but using 3-bromopyruvate n-propyl ester and n-propanol, the following compounds were prepared: 1,2,3,6-tetrahydronitrogen [4, 57] N-propyl ester of indole-5-carboxylic acid; 1H-NMR (CDC13): (Π0.41 (1H, br s), 7.74 (1H, d), 7.35 (1H, s) , 7.56 (1H, d), 7.26 (1H, d) 5 7 · 09 (1Η, m), 5.23 (1Η, br s), 4.11 (2Η, d), 3.54 (2Η, br s), 3.12 (2Η, br s), 1.68 (2Η, m), 0.95 (3H, t); MS (ES): 271 (MH +). B. The title compound is similar In the manner described in Example 2A, 1,2,3,6-tetrahydronitrogen was used to entrain [4,5 hepta] indole-5-carboxylic acid n-propyl ester (compound of Step IXA) and chlorobenzene Made of formazan; 1H-NMR (CDC13): δ 10.55 (lH, brs), 8_07 (lH, s), 7.52-7.58 (4H, m), 7.47 (2H, m), 7.33 (1H, d ), 7.21 (1H, m), 7.12 (1H, m), 4.23 (2H, t), 4.13 (2H, m), 3.28 (2H, m), 1.56 (2H, m), 1 · 40 (3H, t); MS (ES): 375 (MH +) · C. In a similar manner, but replacing benzamidine chloride with an appropriately substituted europium chloride, the following compound was prepared: 3- (4-fluorobenzene Formamyl) -1, 2, 3, 6- Hydrogen-nitrogen enantio [4,5-bH 丨 indole-5-carboxylic acid n-propyl ester; 1H-NMR (CDC13) ... (510.54 (1H, br s), 8.00 (1H, s), 7_62 (2H, m), 7.53 (1H, 85585 -134- 200307684 d) 5 7 · 38 (1H, d), 7.10-7 · 24 (4H, m), 4.23 (2H, t), 4.15 ( 2H, t) 5 3 · 28 (2H, t), 1.51 (2H, m), 0.81 (3H, t); MS (ES): 393 (MH +); 3- (3-p-methoxybenzylhydrazone ) -1,2,3,6-tetrahydronitrogeno [4,5Hepta] -n-propyl 5-carboxylic acid n-propyl ester; 1H-NMR (CDC13): 510.54 (1H, br s), 8 · 09 (1H, s), 7.54 (1¾ d), 7.36 (2H, m), 7.20 (1H, m), 7_05-7 · 13 (4H, m), 4.22 (2H, t) 5 4.12 (2H, t), 3.84 (3H, s), 3.27 (2H, t), 1.67 (2H, m), 0.80 (3H, t); MS (ES): 405 (MH +); 3-Sunflower fluorenyl- 1,2,3,6-tetrahydronitrogeno [4,5-bH 丨 indole-5-carboxylic acid n-propyl ester; 1H-NMR (CDC13): (5 10.55 (1H, br s), 8 · 09 (1H, s), 7.52 (1H, d), 7.38 (1H, d), 7.23 (1H, m), 7.09-7.14 (3H, m), 6.86 (1H, d), 6 · 05 (2H, s), 4.22 (2H, t), 4.17 (2H, t) 3.26 (2H, t), 1.62 (2H, m), 0.85 (3H, t); MS (ES ) · 419 (MH +); 3- (4-chlorobenzyl) ) -L, 2,3,6-tetrahydronitrile indole [4,5-b] indyl-5-folate propyl; MS (ES): 409 (MH +); 3-phenylethylfluorenyl- 1,2,3,6-tetrahydronitrogen benzo [4,5-b], n-propyl ester of indole-5-carboxylic acid; (MS (ES): 389 (MH +); 3- (2,4- Dichlorobenzylidene) -l, 2,3,6-tetrahydronitropyridine [4,5-b] indole-5-carboxylic acid propyl ester; MS (ES): 443 (MH +); 3- (2-Methoxybenzyl) -1,2,3,6-tetrahydronitrocarba [4,5-b] e 丨 indole-5-carboxylic acid propyl ester; MS (ES): 405 (MH + ); 3- (4-methoxybenzylidene) -1,2,3,6-tetrahydronitropyro [4,5-b] indole-5-carboxylic acid propyl ester; MS (ES): 405 (MH +); 1,6-dihydro-2H-nitrogeno [4,5-b] indole-3,5-dicarboxylic acid 3-phenyl ester 5-propyl ester; MS (ES) ·· 491 (MH +); 3- (2,4-dichlorophenylaminomethyl) -l, 2,3,6-tetrahydronitrocarba [4,5Hepta] indole-5-carboxylic acid propyl ester; MS (ES): 448 (MH +); 85585 -135- 200307684 3- (4-methoxyphenazinyl) -l, 2,3,6-tetrahydroazepine [4,5-b; K丨 Propyl indole-5-carboxylic acid; MS (ES): 448 (MH +); 3- (4-chlorobenzenesulfonyl) -l, 2,3,6-tetrahydronitrogen is entrained [4,5 七] Pyridol-5-carboxylic acid propyl ester; MS (ES): 448 (MH +); 3- (3,4-difluorobenzylidene) -1,2,3,6-tetrahydro Nitrogen [4,5-b] eardoline-5-carboxylic acid n-propyl ester; MS (ES): 411 (MH +). Example 6 3 · (4-fluorobenzyl) -8-fluoro Preparation of 1,2,3,6-tetrahydronitrogeno [4,5-8] pyridol-5-carboxylic acid n-propyl ester

A. In a manner similar to that described in Example 1A, using 6-fluoro-tryptamine-HC1 and 3-bromopyruvate n-propyl ester, the following compounds were prepared: 8-fluoro-1, 2, 3, 6- Tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid n-propyl ester MS (ESI) · 289 (MH +). B. In a manner similar to that described in Example 2A, but using 8- Fluoro 1,2,3,6-tetrahydronitrocarba [4,5 hepta] indole-5-carboxylic acid n-propyl ester (compound in Step 骡 A), replacing 1,2,3,6- Tetrahydronitrazine [4,5-b] indole-5-carboxylic acid ethyl ester, and the appropriate compounds were used to prepare the following compounds: 3- (4-fluorobenzyl) -8-fluoro- 1,2,3,6-tetrahydronitrogen benzo [4,5-b] H 丨 indole-5-carboxylic acid n-propyl ester; MS (ES): 411 (MH +); 3- (4-methoxy Benzamidine) each fluoro-U, 3,6-tetrahydronitrogeno [4,5-b] Wind-5-carboxy85585 -136- 200307684 n-propyl acid; MS (ESI): 423 (MH +); and 3- (4-chlorobenzylidene) each fluoro-1,2,3,6-tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid n- Propyl ester; MS (ESI): 427 (MH +) · Example 7 3 (4-fluorobenzylidene) _2_methyl-1,2,3,6-tetrahydronitrogen [4,5 «6] Preparation of indole-5-propanoic acid n-propyl ester

A. 2-methyl-1,2,3,6-tetrahydronitrogen [4,5-b: H-indol-5-carboxylic acid n-propyl ester, in the manner described in Example 1A, Made from α-methyltryptamine and n-propyl 3-bromopyruvate; MS (ESI) · 285 (ΜΗ +) · Β The title compound was prepared in a similar manner as described in Example 2A, using 2 -Methyl-1,2,3,6-tetrahydronitrogeno [4,5_b] indole-5-propanoic acid n-propyl ester (compound in paragraph A) and 4-fluorobenzoic acid chloride MS (ES): 407 (MH +). The racemic sample was subjected to a palm separation. A 10 mm x 250 mm Chiralcel column was used to form a mobile phase with 10% iPrOH / hexane. Thing. C. In a manner similar to that described above, but replacing 4-fluorobenzyl chloride with an appropriately substituted benzyl chloride, the following compounds were prepared: 3- (3,4-difluorobenzyl) -2-Methyl-1,2,3,6-tetrahydronitrocarba [4,5Hepta] indole · 5-carboxylic acid n-propyl ester; MS (ES): 425 (MH +); 3- ( 4-Chlorobenzyl) -2-methyl-1,2,3,6-tetrahydronitrogeno [4,5hepta] indole-5-chinoic acid n-propyl ester; MS (ES) : 423 (MH +); 85585-137-200307684 3- (4-Methoxybenzyl) -2-methyl_1,2,3,6-tetrahydronitrogen [4,5-b] ind Indole-5-carboxylic acid n-propyl ester; MS (ESI): 419 (MH +) · 2-methyl_3- (2-toluenylmethyl) · 1,2,3,6-tetrahydronitrogen [4,5 VII] n-propyl azol-5-carboxylic acid; MS (ESI) · 403 (ΜΗ +); and 3- [2,5-bis (trifluoromethyl) benzyl] -2-Methyl-1,2,3,6-tetrahydronitrogeno [4,5-b] n-propyl indole-5-carboxylic acid; MS (ESI): 525 (MH +) · Example 8 3 (4 • fluorobenzylidene) -2-fluorenyl-8_fluoro_1,2,3,6-tetrahydroazepine [4,5-8] pyridin-5-amino acid n-propyl Preparation of esters

Α · 6-fluoro-3- (2-nitropropionyl) · 1Η · indole was prepared in the following manner. 6-fluoroindole-3-carboxaldehyde (485 mg, 2.97 mmol) Mol), nitroethane (6.0 ml) and ammonium picrate (250 mg, 3.27 mmol). The reaction solution was refluxed for 2 hours. The reaction solution was diluted with EtOAc (100 ml), washed with 条 20 (50 ml x 2), and subjected to liquid separation treatment, dehydrated and dried with Na 2 SO 4, filtered, and under reduced pressure; Chenwei 'provided 560 mg (86% Yield) 6-fluoro-3- (24-based propenyl) _1H- ㈤; 1H NMR (CDC13) δ 11 · 03 (1H, br s), 8.41 (1H, s), 7.63 ( 1H, dd), 7_50 (1H, s), 7_〇6 (1H, dd), 6_92 (1H, t), 2 44 (3H, s); TLC (Si02 plate, 100% dcm) Rf ^ 0.7. B * α • methyl each fluorotryptamine is prepared in the following manner. A solution of 6-fluoro-3- (2-nitropropenyl) -1Η · indole in anhydrous THF (560 mg, 2.54 mmol) 85585 -138- 200307684 at 0 ° C and added dropwise to a stirred mixture of LiAlH4 (480 mg, 12.7 mmol) in THF (40 ml) at 0 ° C. The reaction slurry was stirred under Qin, from o ° c to ambient room temperature, over 3.5 hours. The reaction solution was cooled to 0 ° C again, and then H20 was added dropwise to quench the excess LiAlH4. The reaction suspension was filtered through celite to remove the Al salt. The filtrate was concentrated under reduced pressure, diluted with EtOAc (200 ml), washed with NaCl (50 ml x 2), dried over Na2S04, filtered, and concentrated under reduced pressure to provide 450 mg of α-methyl-6-fluoro Base tryptamine, a thick oil; 6.98-7.04 (2 (, m), 6.87 (1Η, t), 3.29 (1Η, m), 2.87 (1Η, dd), 2.64 (1Η, q), 1.25 (3H, d); MS (ESI): 193 (MH +); TLC (Si02 board, 100% DCM) Rf = 0.1 · C. 2-methyl-8-fluoro-1, 2, 3, 6- Tetrahydronitro-n- [4,5-b] pyridin-5-carboxylic acid n-propyl ester is used in a manner similar to that described in Example 1A, using α-methyl-6-fluorotryptamine and 3-bromo Made from n-propyl pyruvate; MS (ESI) · 303 (ΜΗ +). D · The title compound was prepared in a manner similar to that described in Example 2A, using 2-methyl-8-fluoro-1,2 , 3,6-Tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid n-propyl ester and 4-fluorobenzidine chloride; 111 ^ 111 (〇〇 (: 13) 5 10.47 (111, 8), 7.96 (111, 8), 7.61-7 · 65 (2H, m), 7.41 (1H, m), 7.17 (2H, t), 7.05 (1H, dd) , 6.90 (1H, t), 5.63 (1H, m), 4.17 (2H, m), 4.05 (2H, m), 3.38 (1H, dd), 3.07 (1H, dd), 1.55 (2H m) 5 1.07 (3H, d) 5 0.77 (3H, t); MS (ES): 425 (MH +) · E · In a similar manner as described in steps 骡 A to D, but using the chlorination in step D 3,4-difluorobenzidine replaced 4-fluorobenzidine chloride to prepare the following compound: 3- (3,4-difluorobenzyl) -2-methyl-8-fluoro-1, 2,3,6_tetrahydroazepine [4,5-b] indole-5-carboxylic acid n-propyl ester; MS (ESI): 427 (MH +) 85585 -139- 200307684 Example 9 3- ( Preparation of 4-fluorobenzylidene &gt; 2-ethyl-1,2,3,6_tetrahydronitropyro [4,5-B] indole-5-carboxylic acid n-propyl ester

A. α-Ethyltryptamine is prepared in a manner similar to that described in steps A and B of Example 8 by replacing nitroethane with 1-nitropropane in step 骡 A; MS (ESI): 207 ( MH +). Β 2-ethyl1,2,3,6-tetrahydronitrocarba [4,5Hepta] &lt; n-propyl n--5-carboxylate is similar to that described in Example 1A , But using α-ethyltryptamine to replace tryptamine hydrochloride and 3-bromopyruvate n-propyl ester to replace 3-bromopyruvate ethyl ester; MS (ESI): 303 (MH +). C The title compound was prepared in a manner similar to that described in Example 2A, except that 2-ethyl-1,2,3,6-tetrahydronitrogen was used to incorporate [4,5_b] indole-5-carboxylic acid n-propyl ester. Made by substitution of 1,2,3,6-tetrahydronitrogen with [4,5 hepta] indole-5-carboxylic acid ethyl ester; MS (ESI): 421 (MH +). Accept the racemic sample For palm chromatography, a Chimlcel 10 mm x 250 mm column and a 10% iPrOH / hexane mobile phase were used to obtain two isomers. D. In a manner similar to that described in step C above, but using appropriately substituted benzamidine chloride, replacing 4-fluorobenzyl chloride, the following compounds were prepared: 3- (3,4-di Fluorobenzyl) _2_ethyl-1,2,3,6-tetrahydronitrogeno [4,5Hepta] indole-5-carboxylic acid n-propyl ester; MS (ESI): 439 (MH + ); 3 (4-Chlorobenzyl) -2-ethyl-l, 2,3,6-tetrahydronitrogeno [4,5-b] indole-5-carboxy 85585 -140- 200307684 N-propyl acid esters; MS (ESI) ·· 437 (MH +); and 3 (4-methoxybenzyl) -2-ethyl-1,2,3,6_tetrahydronitrogen [4] , 5Hepta] #-Indole-5-carboxylic acid n-propyl ester; MS (ESI): 433 (MH +) · Example 10 3_ (4_fluorobenzyl) -9-methoxy-1,2,3 Preparation of Ethyl-6-tetrahydronitro [4,5_8] indole-5_resultate

A. The title compound was used in a manner similar to that described in Example 2A, using 9-methoxy-1,2,3,6-tetrahydronitrogen to entrain [4,5Hepta] indole-5-carboxylic acid ethyl ester. Made with 4-fluorobenzidine chloride; 1 H-NMR (CDC13): 510.42 (1H, br s), 7_98 (1H, s), 7.62 (2H, m), 7.28 (1H, m), 7.16 (2H, m), 6.93 (1H, d), 6_88 (1H, dd), 4.24 (4H, m), 3.88 (3H, s), 3.23 (2H, m), 1.23 (3H, t); MS (ES) · 409 (MH +). B. In a similar manner, but using appropriately substituted europium chloride, chloroformate or isocyanate, in place of 4-fluorobenzyl chloride, The following compounds were prepared: 9-methoxy-3-sunflower fluorenyl-1,2,3,6-tetrahydronitrogeno [4,5seven] &lt; ethyl indole-5-carboxylic acid; iH-NMRCCDCL) : ά10.43 (1Η, brs), 8.06 (lH, s), 7.27 (2H, m), 7.12 (2H5 m), 6.93 (1H, d), 6.86 (2H, m) , 6.01 (2H, s) 5 4 · 25 (2H, q), 4.21 (2H, t), 3.88 (3H, s), 3.21 (2H, m), 1.26 (3H, t); MS (ES): 435 (MH +); 3- (2,4-dichlorobenzyl) hexyl-1,2,3,6-tetrahydronitrogen [4,5hepta] indole- Ethyl 5-carboxylate; 3-benzyl-9-methoxy-1 2,3,6-Tetrahydronitrogeno [4,5Hepta] oxindole-5_carboxylic acid ethyl 85585-141-200307684 ester; MS (ES): 390 (M +); 3- (4-chlorobenzene (Methylfluorenyl) -9-methoxy-1,2,3,6-tetrahydronitrocarbazone [4,5Hepta] oxindole-5-carboxylic acid ethyl ester; MS (ES) ·· 390 (MH +) ; 3-Ethyl-9-methoxy-1,2,3,6-tetrahydronitrocarbazone [4,5-b] oxindole-5-carboxylic acid ethyl ester; MS (ES): 329 ( MH +); 9-methoxy-3- (2-methoxybenzylidene) -1,2,3,6 · tetrahydroazepine [4,5VII &gt; 5 丨 indole-5-carboxylic acid Ethyl ester; MS (ES): 421 (MH +); 9-methoxy-3- (3-methoxybenzylidene) -1,2,3,6-tetrahydronitrogen [4,5- b] Ethyl-5-carboxylic acid ethyl ester; MS (ES): 421 (MH +); 9-methoxy-3- (4-methoxybenzylidene) -1,2,3,6-tetrakis Hydrogen-nitrogen benzo [4,5 hepta] oxindole-5-carboxylic acid ethyl ester; MS (ES): 421 (MH +); 9-methoxy-1,6-dihydro-2H-nitrogen benzo [4,5 , 5Hepta] pyrene-3,5-dicarboxylic acid 5-ethyl 3-phenyl ester; MS (ES): 407 (MH +); and 3- (2,4-dichlorophenylamine formamidine) -9-Methoxy-1,2,3,6-tetrahydronitrocarba [4,5_b] indole-5 · carboxylic acid ethyl ester; MS (ES): 474 (MH +) · Example 11 9-Fluorine 3- (4-fluorobenzylidene) _1,2,3,6_tetrahydronitrogeno [4,5-BH indol-5 The preparation

A. The title compound was synthesized in a manner similar to that described in Example 2 using 9-fluoro-1,2,3,6-tetrahydronitrogen p-benzo [4,5-b] 17? Ethyl acetate and ratified 4-fluorobenzyl turtle 85585 -142- 200307684; 1H-NMR (CDC13): δ 10.57 (1Η? Br s) 5 8.04 (1Η5 s), 7.62 (2Η, dd) 5 7.29 (1H, m), 7.16 (3H, m), 6.95 (1H, m), 4.24 (4H, m) 5 3.20 (2H, m), 1.22 (3H, t); MS (ES ): 397 (MH +). B. In a similar manner, but using appropriately substituted europium chloride, chloroformate, or isocyanate, in place of 4-fluorobenzyl chloride, the following compounds were prepared: 9-Fluoro 3- (4-Toluenylmethyl) -1,2,3,6-tetrachlorochrysene and [4,5-b] p5 丨 Homo-5-endoic acid ethyl ester; 1H-NMR (CDC13): δ10 · 57 (1H, br s), 8.14 (1H, s) 5 7 · 49 (2H, d), 7.27 (3H, m), 7.15 (1H, dd), 6.93 (1H, m), 4 23 (4H, m), 3-19 (2H, m), 2.43 (3H, s), 1.22 (3H); MS (ES): 393 (MH +); 3-benzoate-9-fluoro-1, 2,3,6-tetrahydronitrogen appeals to [4,5-b] i 丨 Homo-5-acid acetate; MS (ES): 379 (MH +); 9-fluoro-3_ (3-fluorobenzene Formamyl) -l, 2,3,6-tetrahydronitrile [4, 5-7] Ethyl quinol-5-carboxylate; MS (ES): 397 (MH +); 3- (2,3-difluorobenzyl) -9-fluoro-1, 2, 3, 6 -Tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES): 415 (MH +); 3- (2,4-difluorobenzyl) hexyl -1,2,3,6-tetrahydronitrozine [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES) · 415 (MH +); 3- (2,5-di Fluorobenzyl) -9-fluoro-1,2,3,6-tetrahydronitrogeno [4,5-b] earthin-5-carboxylic acid ethyl ester; MS (ES) ·· 415 ( MH +); 3- (3,4-difluorobenzyl) -9-fluoro-1,2,3,6-tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid Ethyl ester; MS (ES) ·· 415 (MH +); 3- (3,5-difluorobenzyl) -9-fluoro-1,2,3,6 · tetrahydronitrogen [4, 5 Hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 415 (ΜΗ +); 3- (4-chlorobenzoate) dongfluoro-1,2,3,6-tetrahydronitro p-Ping [4,5-b] 啕 -5--5-85585 -143- 200307684 ethyl acetate; MS (ES): 413 (MH +); 3- (2 bucket dichlorobenzylidene) _9 · Fluorine 1,2,3,6-tetrahydronitrogeno [4,5-b] Windole-5-carboxylic acid ethyl ester; MS (ES) ·· 447 (MH +); 9-fluoro-3- (3-Methoxybenzyl) 1,2,3,6-tetrahydronitrocarbazone [4,5-b: N indole-5-carboxylic acid ethyl ester; MS (ES): 409 (M H +); 9-Fluoro-3- (4-methoxybenzylidene) -1,2,3,6-tetrahydronitrogeno [4,5-b] ardol-5-carboxylic acid ethyl ester ; MS (ES): 409 (MH +); 3- (benzo [1,3] dioxo-5-carbonyl) _9_fluoro group_1,2,3,6_tetrahydronitrogen benzo [ 4,5-b] indole-5_carboxylic acid ethyl ester; MS (ES): 423 (MH +); 9 · fluoro-3 · (pyridine-3-carbonyl) -1,2,3,6-tetra Hydrogen and nitrogen [4,5 hepta] &lt; ethyl indole-5-carboxylic acid; MS (ES): 380 (MH +); 9-fluoro_3- (pyridine-4-carbonyl) -1,2, 3,6-tetrahydronitropyre [4,5seven] &lt; ethyl indole-5-carboxylic acid; MS (ES): 380 (MH +); 9-fluoro-3- (4-fluorosulfofluorene -Benzyl) -l, 2,3,6-tetrahydroazepine [4,5Hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 461 (MH +); 9-fluoro 3- (4-nitrobenzylidene) -1,2,3,6-tetrahydronitro, which is [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES): 424 (MH +); 9-fluoro-1,6-dihydro-2H-nitrogeno [4,5 hepta] indole · 3,5-dicarboxylic acid 5-ethyl ester; 3-phenyl ester; MS ( ES): 395 (ΜΗ +); 3- (2,4-dichlorophenylamine formamidine) -9-fluoro-1,2,3,6-tetrahydronitrogen [4,5-b ] Indole-5_carboxylic acid ethyl ester; MS (ES): 463 (MH +). Example 12 9-Gas_3_ (3-fluorobenzyl) -1,2,3,6_tetrahydro And call [4,5; 8] indole Di - Preparation of ethyl several 855855- - 144--200307684

A. The title compound was prepared in a manner similar to that described in Example 2A, using 9-chloro-1,2,3,6-tetrahydronitrogen to incorporate [4,5Hepta] indole-5-carboxylic acid ethyl ester with Made from 3-fluorobenzyl chloride; 1 H-NMR (CDC13): 5 10.61 (1H, br s), 8.07 (1H, s), 7.46 (2H, m), 7.28 (4Η, m), 7.14 (1Η, dd), 4.25 (2Η, q), 4.19 (2Η, t), 3.21 (2Η, t), 1.22 (3H, t); MS (ES): 413 (MH +) · B_ In a similar manner, but using appropriately substituted europium chloride, chloroformate, or isocyanate, in place of 3-fluorobenzyl chloride, the following compounds are prepared: 9-chloro-3- (4-chlorobenzene (Methylamidino) -1,2,3,6-tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid ethyl ester; 1 H-NMR (CDC13): (510.52 (1H, br s), 8 · 04 (1H, s), 7.55 (2H, m), 7.46 (3H, m), 7.29 (1H, d) 5 7 · 14 (1H, dd), 4.26 (2H, q), 4.19 (2H, t), 3.21 (2H, t), 1.23 (3H51); MS (ES): 429 (MH +); 9-chloro-3- (2-p-methoxybenzyl) ) -L, 2,3,6-Tetrahydronitrogeno [4,5 hepta] oxindole-5-carboxylic acid ethyl ester; 1 H-NMR (CDC13) · 5 10.56 (1H, br s), 8 · 05 (1H, br s), 7.48 (2H, m), 7. (1H, d d), 7.26 (1H, d), 7.10 (2H, m), 6.98 (1H, d), 4_21 (2H, br s), 3.90 (2H, br s), 3.24 (2H, br s ), 1 · 21 (3H, br s); MS (ES) ·· 425 (MH +); 9-Gas-3 · (2,5-difluorobenzyl) -1,2,3,6 -Tetrahydronitrogeno [4,5 hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 431 (MH +); 3. · benzylidene-9-chloro-1,2,3, 6-Tetrahydronitrogeno [4,5Hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 395 (MH +); 9-chloro-3- (2,3-difluorobenzidine ) -L, 2,3,6-tetrahydronitrocarba [4,5_b] indole-5-carboxylic acid ethyl ester; MS (ES): 431 (MH +); 85585 -145- 200307684 9-chloro -3- (2,4-difluorobenzylidene) -1,2,3,6-tetrahydroazepine [4,5-bH-butor-5-carboxylic acid ethyl ester; MS (ES): 431 (MH +); 9-chloro-3_ (2,6-difluorobenzylidene) -1,2,3,6-tetrahydronitrogeno [4,5-bH 丨 indol-5-carboxylic acid Ethyl ester; MS (ES): 431 (MH +); 9-chloro_3- (3,4-difluorobenzylidene) -1,2,3,6-tetrahydronitropyrene [4,5 Seven] 4 丨 Ethyl indole-5-carboxylic acid; MS (ES): 431 (MH +); 9-Gas-3_ (3,5_digas benzyl) -1,2,3,6- Tetranitrogen 1? Flat [4,5-1)] 1? 5 丨 1? Wood-5_ carboxylic acid ethyl ester; MS (ES): 431 (MH +); φ 9-chloro -3- (2,4-dichlorobenzylidene) -1,2,3,6-tetrahydroazepine [4,5hepta] pyrene-5-carboxylic acid ethyl ester; MS (ES): 463 (ΜΗ +); 9-chloro-3- (3-methoxybenzylidene) -1,2,3,6-tetrahydroazepine [4,5Hepta] indole-5-carboxylic acid ethyl Esters; MS (ES) ·· 425 (MH +); 9_chloro-3_ (4-methoxybenzyl) -l, 2,3,6-tetrahydronitrogen [4,5-b] Indole-5-carboxylic acid ethyl ester; MS (ES): 425 (MH +); 9-chloro-3- (4-fluorobenzyl) -1,2,3,6-tetrahydronitrogen [4,5Seven] 4 丨 Ethyl-5-carboxylate; MS (ES): 413 (MH +); φ 3- (benzo [1,3] dioxolene-5-carbonyl) -9 -Chloro-1,2,3,6-tetrahydronitrocarba [4,5-b] indh-5-5-acrylic acid ethyl ester; MS (ES): 439 (ΜΗ +); 9_chloro- 1,6-dihydro-2H-nitrogeno [4,5-b] ^ indole-3,5-dicarboxylic acid 5-ethyl ester; 3.phenyl ester; MS (ES): 410 (MH +); 9 -Chloro-3- (2,4-dichlorophenylaminemethylamidino) · 1,2,3,6-tetrahydronitrocarba [4,5hepta] indole-5-carboxylic acid ethyl ester; MS (ES) · 478 (ΜΗ +); and 9-chloro-3- (2-fluorobenzylidene) -1,2,3,6-tetrahydronitrogen is benzo [4,5 七] 啕Ethyl indole-5-carboxylic acid; MS (ES): 413 (MH +). 85585 -146 · 200307684 Example 13 9-Bromo-3- (4-fluorobenzyl) 1 Preparation of 2,4,3,6_tetrahydronitrogeno [4,5tundol_5, 5-acrylic acid ethyl ester

A. The title compound was prepared in a manner similar to that described in Example 2A, using 9-bromo-1,2,3,6-tetrahydronitrocarba [4,5Hepta] indole-5-carboxylic acid ethyl ester and Made from 4-fluorobenzyl chloride; 1H-NMR (CDC13): 610.56 (1H, s), 7.98 (1H, s), 7.56 (3H, m), 7.19 (1H, m), 7. · 09 (2H, m), 4.17 (4H, m), 3.13 (2H, m), 1.13 (3H, t). MS (ESI): 457, 459 (MH +). B. Similar Method, but replacing 4-fluorobenzyl chloride with appropriate benzamidine chloride to prepare the following compounds: 9-bromo_3- (3 • fluorobenzyl) -1,2,3,6-tetra Hydrogen nitrogen benzo [4,5-b] pyridin-5-carboxylic acid ethyl ester; MS (ESI): 457, 459 (MH +); 9-bromo-3- (2-fluorobenzyl)- l, 2,3,6-tetrahydronitrobenzyl [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ESI) ·· 457, 459 (MH +); 9_Bromo_1,2,3,6_tetrahydronitrogeno [4,5hepta] oxindole-5-carboxylic acid ethyl ester; MS (ESI): 439, 441 (MH +); 9-bromo -3- (4-Chlorobenzyl) -1,2,3,6_tetracarbazine benzo [4,5hepta] indole-5-carboxylic acid ethyl ester; MS (ESI) ·· 473,475 (MH +); and 9-bromo-3- (3-chlorobenzylfluorenyl) -i, 2,3,6-tetrahydronitrogen inducing [4,5-b] i Ethyl ester; MS (ESI): 473, 475 (MH +). 85585. 147- 200307684 Example 14 3-Benzylfluorenyl · 8_fluorenyloxy1,2,3,6-tetrahydronitrogen [4] , 5-6] Preparation of adol

Α. The title compound was used in a manner similar to that described in Example 2A to utilize 8-methoxy-1,2,3,6-tetrahydronitrogen to indole [4,5-b] indole-5-carboxylic acid ethyl Esters and benzamidine chloride; 1 H-NMR (CDC13): 510.41 (1H, br s), 7.98 (1H, s), 7.56 (2H, m), 7.52 (1H, m), 7.46 (2H , M), 7.39 (1H, d), 6.86 (1H, d), 6.79 (1H, dd), 4_22 (2H, q), 4.19 (2H, t), 3.86 (3H, s ), 3.23 (2H, t), 1.20 (3H, t); MS (ES): 391 (MH +). B. In a manner similar to that described above, but using appropriately substituted europium chloride, chlorine Formates and isocyanates, replacing benzamidine chloride, to prepare the following compounds: 3-benzylhydrazine-8-methoxy · 1,2,3,6-tetrahydronitrogen is entrained [4,5-b] Benzole-5 ethyl carboxylate; 1 H-NMR (CDC13): 5 10.40 (1H, br s), 7.90 (1H, s), 7.61 (2H, m), 7.40 (1H, d) 5 7 · 15 (2H, m), 6.86 (1H, d), 6.79 (1H, dd), 4.25 (2H, q), 4.19 (2H, t), 3.86 (3H, s), 3.23 (2H, t), 1.23 (3H, t); MS (ES): 408 (M +); 8-methoxy-3- (2,3,4-trifluorobenzyl) -l , 2,3,6-tetrahydronitrogen appeals to [4,5-b] indole-5-carboxylic acid Esters; 1 H-NMR (CDC13): 5 10 · 35 (1H, br s), 7.38 (1H, d), 7.26 (2H, m), 7.12 (1H, m), 7.15 ( 1H, m), 6.85 (1H, d), 6.79 (1H, dd), 4.25 (2H, m) 5 4.19 (2H, t) 5 3.86 (3H, s), 3.23 ( 2H, t), 1.23 (3H, t); MS (ES) · 444 (M +); 3- (2,4-difluorobenzyl), each methoxy group 4,2,3,6 -Tetrahydronitropyrene [4,5-b; Ethyl Ndo-5-carboxylic acid; MS (ES): 427 (MH +); 85585 -148- 200307684 3- (Benzo [1,3] dioxy Woodinene-5-carbonyl) each methoxy-1,2,3,6_tetrahydronitrogen deuterates [4,5 hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 435 (MH + ); 3- (2,4-dichlorophenylamine methylamidino) -8-methoxy-1,2,3,6-tetrahydronitrogero [4,5-b] indole-5- Ethyl carboxylate; MS (ES): 474 (MH +); and 8-methoxy-1,6-dihydro_2H-nitrogeno [4,5Hepta] oxindole-3,5-dicarboxylic acid 5-Ethyl ester; 3-Phenyl ester; MS (ES): 407 (MH +) · Example 15 8_Fluoro-3-benzylfluorenyl1,2,3,6_tetrahydronitrogen [4, Preparation of 5_BH 丨 Indole 5-Carboxylate

A. The title compound was used in a manner similar to that described in Example 2A, using 8-fluoro-1,2,3,6-tetrahydronitrogen to intermole [4,5Hepta] indole-5-carboxylic acid ethyl ester and Made from benzamidine chloride; 1H-NMR (CDC13 Υ δ 10.57 (1H? Br s)? 8.05 (1H? S) 5 7.55 (3¾ m) 5 7.45 (3H5 m), 7.05 (1H, dd), 6 87 (1H, m), 4.22 (4H, m), 3.24 (2H, t), L2 (3H, t); MS (ES): 379 (MH +). B. In a similar manner, but with appropriate substitution Sulfonium chloride, chloroformate or isocyanate, replacing benzamidine chloride, to prepare the following compounds: 8-fluoro_3- (3 • fluorobenzyl) -1,2,3,6-tetrahydro Azine [4,5 hepta] oxindole-5-carboxylic acid ethyl ester; iH-NMRCCDCU) · 5 10.56 (lH, brs), 7.99 (lH, s), 7.44 (2H, m), 7.32 (2H, m), 7 · 24 (1H, m), 7 · 04 (1H, dd) 5 6 · 88 (1H, m) 5 4 · 25 (2H, q), 4 · 19 (2H, t) , 3.24 (2H, m), 1.23 (3H, t); MS (ES): 397 (MH +); 85585 -149- 200307684 8-fluoro-3- (4-fluorobenzyl) -l , 2,3,6-tetrahydronitrogen benzo [4,5-b] Windole-5-carboxylic acid ethyl ester; 1H-NMR (CDC13): (510.46 (1H, br s), 7.97 (1H , S), 7.62 (2H, m), 7.43 (1H, m), 7.1 7 (2H, m), 7.05 (1H, dd), 6_88 (1H, m), 4.25 (2H, q), 4.21 (2H, t), 3.24 (2H, t), 1.25 (3H, t); MS (ES): 396 (M +); 3- (3,4-difluorobenzylidene) -8-fluoro-1,2,3,6-tetrahydronitrogen [4,5 -b] ethyl indole-5-carboxylic acid; 1 H-NMR (CDC13): 510.55 (1H, br s), 7.93 (1H, s), 7.46 (2H, m), 7.35 (1H5 m), 7.25 (1H, m), 7.05 (1H, dd), 6.88 (1H, m), 4.28 (2H, q), 4.19 (2H)? 3.24 (2H51)? 1.25 (3H51); MS (ES): 415 (MH +); _3_ (4-p-methoxybenzylidene) -8-fluoro-1,2,3,6-tetrahydronitrogen [4,5 -bH 丨 indole-5-carboxylic acid ethyl ester; 1 H-NMR (CDC13) ·· δ 10 · 58 (1H, br s), 8.07 (1H, s), 7.59 (2H, m), 7.41 ( 1H, m) 5 7.05 (1H, dd), 6.96 (2H, m), 6.87 (1H, m), 4.26 (2H, q), 4.21 (2H, t), 3. 88 (3H, s), 3.23 (2H, t), 1.24 (3H, t); MS (ES): 409 (MH +); 8-fluoro-3-sunflower Si-1,2,3, 6-tetrahydronitrogenates [4,5-b] W 丨 Homo-5-chinoic acid ethyl ester; 1H-NMR (CDC13): 5 10.57 (lH, brs), 8.06 (lH, s), 7.4 (lH , Dd), 7.10 (2H, m), 7.04 (1H, dd), 6.87 (2H, m) 6.06 (2H, s), 4.27 (2H, q), 4.19 (2H, t), 3.22 (2H, t), 1.26 (3H, t); MS (ES): 422 (M +) ; φ 3- (2,4-dichlorophenylamine formamidine) -8-fluoro-1,2,3,6-tetrahydronitrogeno [4,5-b] indole-5_carboxy Ethyl acetate; 1 H-NMR (CDC13) ·· δ 10.60 (1H, br s), 8.21 (1H, d), 8.13 (1H, s), 7.42 (2H, m), 7.27 (1H, m), 7.05 (1H, d), 6.87 (1H, m), 4.39 (2H, q), 4.1 (2H, m), 3.22 (2H, m) 5 1.41 (3H, t); MS (ES): 462 (MH +); 3-Ethyl-8-fluoro-1,2,3,6_tetrahydronitrogeno [4,5hepta] indole-5 · Ethyl carboxylate; MS (ES): 317 (MH +); 8-fluoro-3- (2-fluorobenzyl) -l, 2,3,6-tetrahydronitrogen [4,5 Seven] Ethyl indole-5-carboxylic acid; MS (ES): 397 (MH +); 85585 -150- 200307684 3- (2,3-—fluoroaspartyl) _8-fluoro-1,2, 3,6-tetrahydroazepine [4,5_b] g 丨 Homo-5-carboxylic acid ethyl ester; MS (ES): 415 (MH +); 3- (2,5-difluorobenzyl) -8-Fluoro-1,2,3,6-tetrahydronitrogeno [4,5-b] ^ indole-5-carboxylic acid ethyl ester; MS (ES): 415 (MH +); 3- (2 , 6-Monofluorobenzyl) -8-fluoro-1,2,3,6-tetrahydronitrogen deuterates [4,5-b] p? 丨 Homo-5-carboxylic acid ethyl ; MS (ES): 415 (MH +); 3- (3,5-monofluorobenzoate) -8-fluoro-1,2,3,6-tetrahydronitrogen [4,5-b] W 丨 Homo-5-carboxylic acid ethyl ester; MS (ES): 415 (MH +); 3- (4-Chlorobenzyl) -8-fluoro-1,2,3,6-tetrahydronitro Phosphoro [4,5-bp? 丨 Homo-5-endoic acid ethyl ester; MS (ES): 413 (MH +); 3- (2,4-dichlorobenzyl) -8-fluoro-1 , 2,3,6-Tetrahydronitrogeno [4,5-b] ^ indole-5-carboxylic acid ethyl ester; MS (ES): 447 (MH +); 8. · Fluoro-3- (2-methyl Oxybenzyl) -1,2,3,6_tetrahydronitrocarbazone [4,5Hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 409 (MH +); 8-fluoro group -3- (3-methoxybenzylidene) -1,2,3,6-tetrahydronitrocarbazone [4,5Hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 409 ( MH +); 3- (2,4_difluoroi benzamidine) -8-fluoro · 1,2,3,6-tetrahydronitrogen appeals [4,5-b] 4 丨 lar-5- Ethyl carboxylate; MS (ES): 415 (MH +); and 8-fluoro · 1,6 · dihydro · 2Η-nitrogeno [4,5Hepta] wormworm-3,5-dicarboxylic acid 5 -Ethyl ester; 3-Phenyl ester; MS (ES): 395 (MH +) · Example 16 3_ethynyl_7_methyl · 1,2,3,6-tetrahydronitrogen [4,5_8] Preparation of ethyl 5,5-butor-5-carboxylate 85585 -151- 200307684

A. The title compound was prepared in a manner similar to that described in Example 2A, using 7-methyl-1,2,3,6-tetrahydronitrogeno [4,5-bH 丨 indole-5-carboxylic acid ethyl ester and Made from acetamidine chloride; 1H-NMR (CDC13): 510.50 (1H, br s) 5 8 · 12 (1H, br s), 7.36 (1H, d) 5 7 · 01 (2H, m), 4.39 (2H, q), 4.01 (2H, m), 3_16 (2H, m), 2.53 (3H, s), 2.39 (3H, s), 1.43 (3H, t); MS (ES): 313 (MH +). B. In a similar manner, but using appropriately substituted europium chloride, chloroformate, and isocyanate, replacing acetamidine chloride, the following compounds were prepared: 3 · (4 · fluorobenzene Methenyl) -7 · methyl_3,1,2,3,6-tetrahydronitrogeno [4,5 hept] ardol-5-carboxylic acid ethyl ester; 1 H-NMR (CDC13): 5 10.49 (1Η, br s), 8.01 (1Η, s), 7.61 (2Η, m), 7.38 (1H, d), 7.16 (2H, m), 7.02 (2H, m), 4.27 (2H, q), 4.21 (2H, t), 3.27 (2H, t), 2.53 (3H, s), 126 (3H, t); MS (ES): 392 (MH +); 3-benzylidene-7-methyl-1,2,3,6-tetrahydronitrocarba [4,5-bHl indole-5-carboxylic acid ethyl ester; MS (ES): 375 (MH +); 3- (2-fluorobenzylidene) -7-methyl-1,2,3,6-tetrahydronitrogeno [4,5hepta] pyridine Ethyl-5-carboxylic acid; MS (ES): 393 (MH +); 3- (3-fluorobenzyl) -7-methyl-1,2,3,6-tetrahydronitrogen [4] , 5Hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 393 (MH +); 3- (2,3-difluorobenzyl) -7-methyl_1,2,3,6 _Tetrahydronitrogero [4,5-b] indole-5_ carboxylic acid ethyl ester; MS (ES): 411 (MH +); 3- (2,4-difluorobenzyl) -7-form 1,2,3,6-tetrahydronitrocarbazone [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES): 411 (MH +); 85585 -152- 200307684 3- ( 2,5-monofluorobenzylidene) _7-methyl_1,2,3,6-tetrahydronitrocarba [4,5-b] p5 丨 ethyl-5-carboxylic acid ethyl ester; MS (ES ): 411 (MH +); 3- (2,6-one-gas benzamidine) _7_methyl-1,2,3,6-tetrahydronitrogen is inferred [4,5_b] W 丨 -5 · carboxyl Ethyl Ester; MS (ES) ·· 411 (MH +); 3- (3,4-monofluorobenzylidene) _7_methyl-1,2,3,6-tetrahydronitropyridine [4 , 5-b] p? 丨 -5-carboxylic acid ethyl ester; MS (ES) ·· 411 (MH +); 3- (3,5_-murine benzyl) -7-methyl-1, 2,3,6-tetrachloronitrogen evokes ethyl [4,5-b] p5 budol-5-carboxylic acid; MS (ES): 411 (MH +); φ 3_ (4_benzylbenzyl) ) -7-methyl-1,2,3,6-tetrahydronitrocarba [4,5-b] p? 丨 -5--5-acid ethyl ester; MS (ES): 409 (MH +); 3- (2,4-monomurinobenzoate) _7_methyl-1,2,3,6-tetrakiscarpine [alpha] Ben [4,5-b] 1 ^ 丨 Homo-5-carboxylic acid ethyl ester ; MS (ES): 443 (MH +); 3- (2-methoxybenzyl) -7-methyl-1,2,3,6-tetrachloronitrogen [4,5-b] 17 ? 丨 Homo-5-acrylic acid ethyl ester; MS (ES): 405 (MH +); 3- (3-methoxybenzylidene) -7_fyl · 1,2,3,6-tetrahydronitrogen [4,5Hepta] Ethyl indole-5-carboxylic acid; MS (ES): 405 (ΜΗ +); # 3- (4-methoxybenzyl) -7-methyl-1,2, 3,6_tetrahydronitrobenzyl [4,5hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 405 (MH +); 3_ (benzo [1,3] dioxolene- 5-carbonyl) -7-methyl_1,2,3,6-tetrahydronitrogen is eh [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES): 419 (MH +); 7-Methyl-3- (4-nitrobenzylidene) -1,2,3,6-tetrahydronitrocarba [4,5hepta] indole-5-carboxylic acid ethyl ester; MS (ES ): 420 (MH +); 7-methyl-3- (4-methyl-3-nitrobenzoate) -1,2,3,6-tetraazanitrogen degenerates [4,5-1)] # 丨 荟 _5_carboxylic acid ethyl ester; MS (ES): 434 (MH +); 85585 -153- 200307684 3_ (4-methoxycarbonyl-benzylidene) -7-methyl-1,2,3 , 6 · Tetrahydronitropyrene [4,5Hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 433 (ΜΗ +); 7-methyl-1, 6-Dihydro_2H-nitrogeno [4,5_b] indole-3,5-dicarboxylic acid 5-ethyl ester; 3-phenyl ester; MS (ES): 391 (MH +); 3- (2, 4-Dichlorophenylamine formamidine) -7-methyl_1,2,3,6_tetrahydronitrogeno [4,5hepta] oxindole-5-carboxylic acid ethyl ester; MS (ES) : 458 (MH +); Example 17 3_ (4_fluorobenzyl) -1,2,3,6-tetrahydronitrogen [4,5_8], 5 丨 5-5,8 · dicarboxylic acid di Preparation of ethyl ester

A. A suspension of methyl 3-formamyl indole metabolite (10 g, 49.2 mmol) and ammonium acetate (2 g) in nitromethane (50 ml) was heated to reflux, 1 hour. After cooling, the solid was collected by filtration, washed with methanol, and dried under a local vacuum to obtain 3- (2 '· nitroethylfluorenyl) · 6-carboxylic acid methyl ester (η · 2 g). The whole was then subjected to hydrogenation in ethanol (100 ml) in the presence of 5% Pd / C (2 g) at 40 psi hydrogen for 2 hours. The catalyst was then removed by filtration and washed with ethanol. The solvent was evaporated under high vacuum to obtain tryptamine methyl methacrylate (7.76 g), which was used in the next step without further purification. Β, 1,2,3,6-tetrahydronitrocarba [4,5-b] W 丨 5,8-diacetic acid diethylammonium is a transesterification product similar to the method described in Example 1A, However, tryptamine hydrochloride is replaced by tryptamine-6-carboxylic acid methyl ester. 85585 -154- 200307684 C. The title compound was used in a manner similar to that described in Example 2A to i [2,3,6-tetrahydronitro] to indole [4,5-b] indole-5,8-dicarboxylic acid. Made from diethyl acid and 4-fluorobenzidine chloride; 1 H-NMR (CDC13): 5 10.78 (1H, bi * s), 8.13 (2H, m), 7.81 (1H, m ) 5 7.63 (2H, m), 7.53 (1H, d), 7.17 (2H, m), 4.39 (2H, q), 4.26 (4H, m), 3.28 (2H, t), 1.42 (3H, t), 1.23 (3H, t); MS (ES): 451 (MH +). Example 18 9_ (4-methoxyphenyl) -1,2,3,6_tetrahydronitrogen [ 4,5-B], Preparation of 5-oxindole-5-carboxylic acid ethyl ester

Α_Bromo-1,2,3,6-tetrahydronitrile entrains [4,5-b] indole-5-carboxylic acid ethyl ester (0.20 g, 0.60 mmol) and 4-formaldehyde In a stirred solution of oxyphenyldihydroxyborane (0.23 g, 1.5 mmol) in DME / EtOH (1: 1, 12 ml), 2.1 ml of a 1M Na2C03 solution and Pd ( OAc) 2 (27 mg). The reaction mixture was heated at 80 ° C and A for 1 hour and monitored by LC-MS. The solution was diluted with DCM (20 mL) and washed with brine. The aqueous phase was extracted twice with DCM (20 mL). The combined organic phases were dried over Na2S04 and concentrated. The crude product was purified on a silica gel by flash chromatography and dissolved in EtOAc-hexane (0-30%) to give the title compound (0J36 g) as a pale yellow solid; 1H-NMR (CDC13): 5 10.41 ( 1H, s), 7.73 (1H, d), 7.50 (3H, m), 7.29 (1H, d), 7.21 (1H, d), 6.90 (2H, m), 5.23 (1H, s), 4.20 (2H, dd), 3.76 (3H, s), 3.55 (2H, m), 3.12 (2H, m), 1_26 (3H, t); MS (ESI): 363 (MH +). 85585 • 155- 200307684 Β · In a manner similar to that described in Example 2A, but using 9- (4-methoxyphenyl) -1,2,3,6-tetrahydroazepine and [4,5-b ] Indrum-5-acrylic acid ethyl ester, replacing 1,2,3,6-tetrahydronitrogen with [4,5-b] indole-5-carboxylic acid ethyl ester, prepared the following compound: 3- (4 -Fluorobenzyl) -9- (4-methoxyphenyl) -1,2,3,6-tetrahydronitrogeno [4,5-bH indole-5-carboxylic acid ethyl ester; 1 H- NMR (CDC13) ·· δΐθ. 46 (1H, s), 8.06 (2H, m), 7.55 (4H, m), 7.08 (4H, m) 5 6.92 (2H, m), 4.18 (4H, m) 5 3.79 (3H, s), 3.23 (2H, m), 1.18 (3H, t); MS (ESI): 485 (MH +) As described in the above, but using the appropriate replacement The benzamidine chloride replaced 4-fluorobenzyl chloride to prepare the following compounds: 3- (3-fluorobenzyl) -9- (4-methoxyphenyl) -1,2,3,6- Tetrahydrozine appeals to [4,5 hepta] oxindole-5-carboxylic acid ethyl ester; MS (ESI): 485 (MH +); 3- (2-fluorobenzyl) -9- (4-T oxygen Phenyl) -l, 2,3,6-tetrahydronitrogen deuterates [4,5 · 1)] β 丨 Homo-5-acrylic acid ethyl ester; MS (ESI): 485 (ΜΗ +); 3-benzene Methylfluorenyl-9- (4 • methoxyphenyl) -1,2,3,6-tetrahydroazepine [4,5hepta] pyrene-5-carboxylic acid ethyl ester; MS (ESI): 467 (MH +); 3- (4-methoxybenzoate) -9- (4-methoxyphenyl) -1,2,3,6-tetrahydroazepine [4,5-b] indole- Ethyl 5-carboxylate; MS (ESI) ·· 497 (MH +); 3 · (4-chlorobenzylidene) _9 · (4-methoxyphenyl) · 1,2,3,6_tetra Hydrogen and nitrogen enzymatic [4,5 hepta] indole-5-carboxylic acid ethyl ester; MS (ESI): 501 (ΜΗ +); 3- (3-chlorobenzylidene) _9- (4-methoxy Phenyl) -1,2,3,6-tetrahydronitrogeno [4,5Hepta] indole-5-carboxylic acid ethyl ester; MS (ESI) · 501 (MH +); and 3-acetamyl -9- (4-methoxyphenyl) -l, 2,3,6-tetrahydroazepine [4,5 hepta] indole-5-carboxylic acid ethyl ester; MS (ESI): 405 (MH + ) · D · Similar to Step 骡 A, but using 3-methoxyphenyl Hydroxyborane 85585 -156- 200307684 replacing 4-methoxyphenyldihydroxyborane to prepare the following compounds: 9- (3-methoxyphenyl) -1,2,3,6-tetrahydronitrogen [4] , 5-b: Ethyl N-dodec-5-carboxylic acid; MS (ESI): 363 (MH +). E. In a manner similar to that described in Example 2A, but using 9- (3-methoxyphenyl)- 1,2,3,6-tetrahydronitrogenates [4,5-b] K | Homo-5-carboxylic acid ethyl ester, replacing 1,2,3,6-tetrahydronitrogenates [4,5- bH 丨 Indole-5_carboxylic acid ethyl ester to prepare the following compounds: 3- (4-fluorobenzyl) -9- (3-methoxyphenyl) -1,2,3,6-tetrahydroazepine And [4,5 七] # 丨 indole-5-carboxylic acid ethyl ester; 1 H-NMR (CDC13): 5 10.52 (1H, s), 7.97 (1H, s), 7_65 (1H, s), 7 · 57 (2H, m), 7.38 (2H, m), 7.11 (3H, m), 6.80 (1H, m), 4.18 (4H, m), 3.82 (3H, s), 3.24 (2H, m), 1.18 (3H, t); MS (ESI): 485 (MH +). F. In a manner similar to that described in step E, but using appropriately substituted chlorobenzene Formamidine replaced 4-fluorobenzyl chloride to prepare the following compounds: 3- (3-fluorobenzyl) -9- (3-methoxyphenyl) -1,2,3,6_tetrahydroazepine Benzo [4,5-b; ethyl ndo-5-carboxylate; MS (ESI): 485 (MH +); 3- (2-fluorobenzylidene) -9- (3-methoxyphenyl) -1,2,3,6-tetraargonium hydride [4,5-b: h 丨 indol- Ethyl 5-carboxylate; MS (ESI) · · 485 (MH +); and 3-Ethylpyrene (3-methoxyphenyl) -1,2,3,6-tetrahydronitrogen [4, 5VII] Ethyl-5-carboxylic acid ethyl ester; MS (ESI): 405 (MH +) · G. In a similar manner to step A, but using methoxyphenyl diboron to replace 4-oxobenzene Dihydroxyborane to prepare the following compounds: 9- (2-methoxyphenyl) -1,2,3,6-tetrahydroazepine [4,5Hepta] indole-5_carboxylic acid ethyl ester; MS (ESI): 363 (MH +). Η. In a manner similar to that described in Example 2A, but using 9_ (2-methoxyphenyl) -1,2,3,6-tetrahydronitrogen [4, 5-b] W ethyl methanoate, replacing 丨, 2,3,6-tetrahydrozine 85585 -157- 200307684 Accompanied by [4,5-b; N indole-5-carboxylic acid ethyl ester, to prepare the following compounds : 3- (4-Fluorobenzyl) dong (2-methoxyphenyl) -1,2,3,6-tetrahydronitrocarba [4,5Hepta] zole-5-carboxylic acid ethyl ester 1H-NMR (CDC13): 510.49 (1H, s), 7.97 (1H, s), 7.59 (3H, m), 7.36 (3Η, m), 7.27 (1Η, m), 7.12 (2Η, m), 6.98 (2Η, m), 4.20 (4Η, m), 3.78 (3H, s), 3.34 ( 2H, m), 1 · 20 (3H, t); MS (ESI): 485 (MH +) · I · In a manner similar to that described in step 骡 H, but replacing the 4-fluorobenzene chloride with ethyl chloride Formazan, the following compounds are prepared: 3-Ethyl-9- (2 • methoxyphenyl) -1,2,3,6-tetrahydronitrogeno [4,5-b] pyridin-5-carboxy Ethyl Ester; MS (ESI): 405 (MH +) · Example 19 3- (4-Fluorobenzyl) -2-methyl_1,2,3,6_tetrahydronitrogen [4,54 】 Preparation of indole · 5-acrylic acid ethyl ester

A. 2-methyl_1,2,3,6_tetrahydronitrogeno [4,5-b &gt; 5 indole-5-carboxylic acid ethyl ester is prepared in a manner similar to that described in Example 1A via It is made by replacing 2-tryptamine hydrochloride with tryptophan hydrochloride. B. The title compound was prepared in a manner similar to that described in Example 2A, using 2-methyl-1,2,3,6-tetrahydronitrogen to instill [4,5Hepta] indole · 5-carboxylic acid ethyl ester with Made from 4-fluorobenzyl chloride; 1H-NMR (CDC13) · δ 10.44 (1Η, br s), 8.01 (1Η, s), 7.63 (2Η, m), 7.52 (1H, d), 7.39 (1H, d), 7.24 (4H, m), 5.61 (1H, br s), 4.22 (2H, m), 3.43 (1H, dd), 3.10 (1H, dd), U9 (3H, t) , 1.06 (3H, d); MS (ES) · 393 (MH +). C. In a manner similar to that described above, but using appropriately substituted chloride 85585 -158- 200307684 醯 instead of chloride 4 -Fluorobenzine to prepare the following compound: 3-benzylmethyl-2-methyl-1,2,3,6-tetrahydronitrogeno [4,5_bH 丨 indole-5-carboxylic acid ethyl ester; 1H -NMR (CDC13) ... δ 10.44 (1H, br s), 8_09 (1H, s), 7.59 (2H, m), 7.51 (4H, m) 5 7.31 (1H, d), 7.19 (1H, m), 7.10 (1H, m), 5.61 (1H, m), 4.18_4 · 27 (2H, m), 3.43 (1H, dd), 3.10 (1H, d), 1_15 ( 3H, t), 1.06 (3H, d); MS (ES): 375 (MH +); 3- (chlorobenzylidene) -2-methyl-1,2,3,6 · tetrahydroazepine Benzo [4,5_b] indole-5-carboxylic acid ethyl Esters; 1H-NMR (CDC13): 5 10.43 (1H, br s), 7.99 (1H, s), 7.54 (3H, m), 7.47 (2H, m), 7_38 (1H, d), 7 · 20 (1H, m), 7.11 (1H, m), 5.59 (1H, m), 4.15-4.30 (2H, m), 3.43 (lH, dd), 3.10 (lH, dd), 1.20 (3H, t), 1.06 (3H, d); MS (ES): 409 (MH +); and 2-methyl-3-sunflower fluorenyl-1,2,3,6-tetrahydronitrogen [4,5_b] Indole-5-carboxylic acid ethylm; 1H-NMR (CDC13): δ 10.45 (1H5 br s), 8.10 (1H, s) 57.51 (1H, d) 5 7.38 (1H5 d), 7.15 (4H, m) , 7.20 (lH, d), 6.07 (lH, d), 6.06 (lH, d), 5.58 (lH, m), 4.17-4 · 33 (2H, m), 3.40 (1H, dd), 3.08 (1H , Dd), 1.20 (3H, t), 1.05 (3H, d); MS (ES): 419 (MH +).

Example 20 Preparation of 2-ethyl_3_sunflower fluorenyl-tetrahydroazepine [4,5 · Β] Θ1 indole-5_carboxylic acid ethyl ester

Α · Make 3- (2'_ethyl-2, · nitroethylfluorenyl) indole (2.5 g, 1L5 millimolar, made according to the literature procedure: Young (1958) J · k: 3493-3496) in The ethanol 85585 -159- 200307684 solution was hydrogenated under 40 psi hydrogen in the presence of 10% Pd / C (0.5 g) for 16 hours. The catalyst was removed by filtration and washed with ethanol. The solvent was removed and The crude was dissolved in ethanol (5 ml). The solution was acidified with aqueous HC1 (1 N, 30 ml). The solution was extracted with toluene (3 x 50 ml). The aqueous layer was concentrated under high vacuum to give 2-ethyl Serotonin hydrochloride (0-74 g) was used without further purification. B. Ethyl_1,2,3,6_tetrahydronitrogeno [4,5-b] pyridin-5 · benzyl Ethyl acetate was prepared in a manner similar to that described in Example 1A, using 2-ethyltryptamine hydrochloride. C. The title compound was prepared in a manner similar to that described in Example 2A, using 2-ethyl-1, Made from 2,3,6-tetrahydronitrile [4,5Hepta] indole-5_carboxylic acid ethyl ester with chlorinated sunflower pyrene. 1H_NMR (CDC13): 6 10.38 (lH, brs), 8.15 (lH , S), 7.52 (lH, d), 7.37 (1H, d), 7.10 (4H, m), 6.88 (lH, d), 6.0 7 (lH, d), 6.06 (lH, d), 5.34 (lH, m), 4.16-4 · 33 (2H, m), 3.53 (1H, dd), 3.00 (1H, dd), 1.29- 1.45 (2H, m), 1.24 (3H, t), 0.81 (3H, t); MS (ES): 433 (MH +). Example 21 3_ (4_fluorobenzylidene H, 2, Preparation of 3,6-tetrahydronitropyrene [4,5 · ΒΗ 丁-5-carbonthio acid 0-ethyl

A. In a solution of 1,2,3,6-tetrahydronitrogenated [4,5 hepta] indole-5-carboxylic acid ethyl ester (0.51 g, 2 mmol) in toluene (20 ml) Add LawessOn's reagent (1.45 g '3.6 mmol). The resulting suspension was heated to reflux under nitrogen for 85585 -160- 200307684 over 24 hours. The solvent was evaporated to obtain the crude product, which was purified by column chromatography on silica gel, and dissolved in MeOH-DCM (1: 19) to obtain 1,2,3,6_tetrahydronitrogenated [4,5- bH 丨 Indole-5 · Carbothioic acid 0-ethyl ester; (27 mg); MS (ES): 273 (MH +). B · In a manner similar to that described in step 2A, but using benzyl ι, 2 , 3,6-Tetrahydronitrogeno [4,5Hepta] indole-5-carbothioic acid 0-ethyl ester, replacing 1,2,3,6-Tetrahydronitrogeno [4,5Hepta] Indole-5-carboxylic acid ethyl ester to make the title compound; NMR (CDCl3): 9.76 (1H, s), 7.95 (1H, s), 7.64 (2H, m), 7.54 ( 1H, d), 7.37 (1H, d), 7.11-7.24 (4H, m), 4.65 (2H, m), 4.23 (2H, t), 3.27 (2H, t), 1.40 ( 3H, t). MS (ES): 395 (MH +) _ Example 22 3_ (4-fluorobenzylfluorenyl) ^. Preparation of tetrahydronitrile

A. 1,2,3,6-tetrahydronitrogenates [4,5 VII] tons of methyl 5-metanoate in a manner similar to that described in Example 1A, but using 3-bromopyruvate Made by ester substitution of ethyl bromopyruvate; MS (ES): 243 (MH +). B. The title compound was synthesized in a manner similar to that described in Example 2A using 1,2,3,6-tetrahydronitrogen [4,5_b] Indole-5-carboxylic acid methyl ester (Kuehne et al. (1985) / Org. CAem. 50: 919-924) and 4-fluorobenzidine chloride; 1h-NMR (CDC13) : 5 10.51 (1H, br s), 7.99 (1H, s), 7.62 (2H, m), 7.53 (1H, d), 7.23 (1H, d), 7.10-7.24 (4H, m) , 4.22 (2H, t), 3.80 (3H, s), 3.27 (2H, m); MS (ES) · 365 (MH +) · C. In a manner similar to step B, but by using Appropriate europium chloride, chloroformate or isocyanate to replace the gasification of 4-fluorobenzylhydrazone to prepare the following compounds: 85585 -161- 200307684 Methyl [4,5-b] W-dod-5-carboxylic acid; MS (ES) • 347 (MH +); 3-Ethyl-1,2,3,6-tetrahydronitrogen [4, 5 Hepta] methyl-5-carboxylate; MS (ES): 381 (MH +); 3- (4-chlorobenzyl) -1,2,3,6-tetrahydronitrogen [ 4,5-b] methyl indole carboxylate; MS (ES): 285 (MH +); 3- (2,4-dichlorobenzyl) -l, 2,3,6-tetrahydroazepine Benzo [4,5-b] indole-5-carboxylic acid methyl ester; MS (ES): 415 (ΜΗ +); φ 3_ (4-tert-butyl-benzylidene) -1,2, 3,6-tetrahydronitrocarbazone [4,5Hepta] indole-5_carboxylic acid methyl ester; MS (ES): 403 (ΜΗ +); 3- (toluenesulfonyl) -1,2, 3,6-Tetrahydronitrogeno [4,5Hepta] indole-5-carboxylic acid methyl ester; MS (ES): 397 (MH +); 3- (4-Third-butyl-benzoic acid group) ) 1,2,3,6 · Tetrahydronitrogen appeals to [4,5-b] 1 ^ 丨 -5_metamate; MS (ES): 439 (MH +); 3- (2_ 甲Oxybenzyl) -1,2,3,6-tetrahydronitrocarbazone [4,5-b] pyridin-5-carboxylic acid methyl ester; MS (ES): 377 (MH +); · 3- (3-Methoxybenzyl) -1,2,3,6-tetrahydronitrocarbazone [4,5-b] Windole-5-carboxylic acid methyl ester; MS (ES): 377 (MH +) ; 3- (4-methoxybenzylidene) -l, 2,3,6-tetrahydronitropyro [4,5-b] indole-5-carboxylic acid methyl ester; MS (ES): 377 (MH +); Example 23 Preparation of 1,2,3,6-tetrahydronitrogeno [4,5-B] ^ dol_S_metanoic acid

〇 &lt; 〇H 85585 -162- 200307684 A. 1,2,3,6-tetrahydronitrogen entrains [4,5_b] indole-5_carboxylic acid methyl ester (1.21 g, 5 mmol) ), A mixture of di-tertiary-butyl dicarbonate (1.69 g, L5 equivalent) and diisopropylethylamine (1.3 ml '1.5 equivalent) in benzene, heated to reflux in a Dean_Stark gas cylinder, 48 hours. After cooling, the solvent was removed and the crude product was re-dissolved in DCM and passed through a silica packed column and dissolved in DCM. Evaporation of the solvent yielded a gum-like product (1,6-dihydro-2H-nitrogen-infused [4,5-b] W 丨 Homo-3,5-dicarboxylic acid 3-third-butyl ester 5-methyl ester) ; IH-NMR (CDCl3): (no. 52 (lH, brS), 8.40 (1H, s), 7.47 (2H, d), 7.34 (1H, m), 7.15 (1H, dd), 7.07 (1H, dd), 3.97 (2H, t) 5 3.87 (3H, s), 3.14 (2H, t) 51 · 57 (9H, s) 5 1.52 (3H, t). B. In 1,6 · dihydro · 2Η · nitrogeno [4,5-b; Hh to-3,5-dicarboxylic acid 3. tertiary-butyl ester 5-methyl ester (0.293 g, 0.62 To a solution of mol) in MeOH (4 mL), 4NNaOH (2 mL) was added and the mixture was heated under nitrogen for 5 hours. After cooling, the reaction mixture was diluted with water and extracted with EtOAc. AcOH The aqueous layer was acidified. The precipitate was collected by filtration, washed with water and ether, and dried under high vacuum to give the title compound (70 mg); 1H-NMR (DMSO-d6): 5 11 · 40 ( 1H, s), 10.73 (1H, br s), 7.83 (1H, m), 7.73 (2H, d), 7.38 (1H, m), 7.25 (1H, m), 6.88 (2H, m), 3.45 (2H, t), 3.87 (3H, s), 3.2.98 (2H, t), MS (ES): 229 (MH +). Example 24 3- ( 4-fluorobenzene Wine-yl) -5- (4,5-dihydro-2-yl-Jun Yin) -l, 2,3,6- tetrahydro-N # and [4,5-B] Preparation of voice wail

85585 -163- 200307684 A. In 3_ (4-fluorobenzylidene) -l, 2,3,6-tetrahydronitrocarba [4,5_b] indole-5_carboxylic acid (176 mg, 0.1 (50 mmol) in a stirred solution of DCm (5 ml, anhydrous), CDI (81 mg, 0.5 mmol) was added. After 1 hour, ethanolamine (60 μl, 1.0 mmol) was added to the reaction mixture, and stirring was continued. After 2 hours, the solution was diluted with CHCMIO100 ml), washed with h20 (100 ml) and brine, then dehydrated (Na2SO4), and concentrated to obtain its corresponding 2 ####### of ethyl amine intermediate ( 0.20 g, quantitative) 'was a white solid, which was used in the next step without purification; MS (ESI): 396 (MH +). B_ This intermediate (Π 5 mg, 0.44 mmol) was in CHC13 (4 ml , Anhydrous) in the stirred suspension, at ambient temperature, drop thionyl chloride disulfide (73 μl, 1.0 mmol). After 1 hour, the reaction mixture was diluted with CHCl3 (4 mL), and 2N NaOH (4 mL) and tetrabutylammonium trioxide (5 mg) were added. After 16 hours, the organic layer was separated, concentrated under reduced pressure, and purified by chromatography on silica gel, and dissolved in EtOAc-DCM (0: 100 to 25:75) to give the title compound (8 mg) as a yellow solid 1H-NMR (CDC13): 5 11.74 (1H, s), 7.66 (1H, br s) 5 7.60 (2H, m), 7.54 (1H, d), 7.42 (1H, d), 7.20 (1H, app t), 7.14 (2H, app t), 7.11 (1H, app t), 4.19-4.28 (4H, m), 4.12 (2H, m), 3.29 (2H, dd); MS (ESI): 376 (MH +). B. In a similar manner, but replaced with 2-amino-2-methylpropanol, 1-amino-2 · propanol, or 1-amino-2-butanol Ethanolamine to prepare the following compound: 5- (4,4-dimethyl-4,5-dihydrohumazol-2-yl) -3- (4-fluorobenzylhydrazine) -1,2,3,6 -Tetrahydronitrogen is benzo [4,5 hepta] indole; 1H-NMR (CDC13): 511.77 (1H, s), 7.64 (1H, br s), 7.61 (2H, m), 7.54 (1H, d) 5 7.44 (1H, d), 7.21 (1H, app t), 7.08-7.17 (3H, m), 4.21 (2H, app t), 3.92 (2H, s), 3.28 (2H, dd) 1,41 (6H, s); MS (ESI) · 404 85585 -164- 200307684 (MH +); 3- (4-fluorobenzylsilyl) -5- (5-methyl-4,5- Dihydro slogan Jun · 2-based -1,2,3,6_tetrahydronitropyrene [4,5seven] antholin; MS (ESI): 390 (MH +); and 5- (5-ethyl-4,5-dihydro slogan 唆_2_yl) -3- (4-fluorobenzoate) -1,2,3,6_tetrahydronitropyro [4,5seven] indole; MS (ESI): 404 (ΜΗ +) · Example 25 Preparation of 1,2,3,6_tetrahydroazepine [4,5-B] &lt; Indole-2,5_dicarboxylic acid diethyl ester

In a manner similar to that described in Example 1A, but replacing the tryptophan hydrochloride with the appropriate tryptophan-methyl-HC1, the following compounds were prepared: 1,2,3,6-tetrahydronitrogeno [4,5- b] indium_2,5-dicarboxylic acid diethyl ester; ^ -NMR (CDC13): δ 10.44 (1H? br s), 7.86 (1H, d), 7.48 (1H? m) 5 7.33 (1H, d) 5 7.09 (2H5 m), 6.10 (1H, d), 4.29 (4H, m), 4.10 (1H, m) 5 3.84 (1H, d), 2.97 (1H, dd), 1.33 ( 6H, m); MS (ES): 329 (MH +); 1,2,3,6-tetrahydronitrogen is [4,5Hepta] indhar-2- (R), 5-dicarboxylic acid diethyl Esters MS (ESI): 329CMH + :); and 1,2,3,6-tetrahydronitrogen is [4,5 hepta] indole-2- (8), 5-dicarboxylic acid diethyl ester. Example 26 [Example 21 3- (4-fluorobenzyl) _1,2,3,6-tetrahydronitro #benzo [4,5-: 8] &lt; Homo_2,5_ diethyl dicarboxylate Preparation 85585 • 165- 200307684

A. The title compound is similar to that described in Example 2A, but using the compound of Example 25, replacing 1,2,3,6-tetrahydronitrogen with [4,5 七] radol-5-carboxylic acid ethyl Esters are made of: 3- (4-fluorobenzyl) -1,2,3,6-tetrahydronitrocarba [4,5 七] 4 丨 Homo_2,5-diacetic acid diethyl ester; W-NMRCCDCIO: 5 10.21 (lH, brs), 8.24 (lH, s), 7.72 (2H, m), 7.55 (1H, d), 7.33 (1H, m), 7.19 (3H, m) 5 7.10 (1H, m), 6.23 (1H, m), 4.19 (2H, m), 4.09 (1H, dd), 3.82 (2H, q), 3.07 (1H, dd), U7 (3H , T), 0.73 (3H, t); MS (ES): 451 (MH +); 3- (4-fluorobenzylhydrazyl) -l, 2, 3, 6-tetrahydronitrogen [4,5 -b; K, indole-2 (R), diethyl 5-dicarboxylate; MS (ESI): 451 (MH +); and 3- (4-fluorobenzyl) -1, 2, 3, 6-tetrahydronitrogeno [4,5Hepta] indole-2CD, 5-dicarboxylic acid diethyl ester; MS (ESI): 451 (MH +) · B. In a similar manner, but using appropriately substituted chlorine Substituted 4-fluorobenzidine chloride with hydrazone to prepare the following compounds: 3 · benzylidene-1,2,3,6_tetrahydronitrogeno [4,5-b] pyridin-2,5- Diethyl dicarboxylate; 1H-NMR (CDC13) · 5 10.22 (1H, br s), 8.30 (1H, s), 7.66 (2H, m), 7.44 (4H, m), 7.32 (1H, d), 7.17 (1H, m), 6.25 (1H, m), 4.16 (2H, m), 4.09 (1H, dd), 3.82 (2H, q), 3.07 (1H, dd), 1.12 (3H, t), 0.73 (3H, t); MS (ES): 433 (MH +); Benzene [4-, 5-seven &gt;?] indole-2,5-dicarboxylic acid diethyl ester with 3-sunflower fluorenyl-1,2,3,6-tetrahydronitrogen 1H-NMR (CDC13): (510.44 (lH, brs), 8.33 (lH, s), 7.52 (lH, d), 7.34 85585 -166- 200307684 (1H, d), 7.25 (1H, m) , 7.14-7.19 (2H, m), 7.11 (1H, m), 6.90 (1H, d), 6.19 (1H, m), 6.08 (2H, m), 4.24 ( 2H, m), 4_08 (1H, dd), 3.82 (2H, q), 3.06 (1H, dd), 1.22 (3H, t), 0.73 (3H, t); MS (ES) ·· 477 (MH +). 3- (2,4-Dichlorobenzylidene) -l, 2,3,6-tetrahydronitrogen [4,5Hepta] pyridin-2,5_dicarboxylic acid di Ethyl ester; MS (ES): 501 (MH +); 3- (4-nitrobenzylidene) -1,2,3,6-tetrahydronitrogeno [4,5-b] Wdol-2 Diethyl 5,5-dicarboxylate MS (ES): 478 (MH +);

3- (3-methoxybenzylidene) -1,2,3,6-tetrahydronitropyrene [4,5-b] ,? indol-2,5-dicarboxylic acid diethyl ester; MS (ES): 463 (MH +); 3- (4-methoxybenzylidene) -1,2,3,6-tetrahydronitrogen [4,5-b] indole-2,5-di Diethyl carboxylic acid; MS (ES): 463 (MH +); and 3- (4-chlorobenzylidene) -1,2,3,6_tetrahydronitrogen [4,5-1] ] Benzin-2,5-dicarboxylic acid diethyl ester; MS (ES): 467 (MH +). Example 27

Preparation of 8-bromo_1,2,3,6_tetrahydronitrogeno [4,54] diazine-2,5-dicarboxylic acid diethyl ester and its modification

A. 8-bromo-I, 2,3,6 · tetrahydroazepine [4,5 hepta] indole-2,5-dicarboxylic acid diethyl ester was used in the manner described in Example 1A. Made from 6-bromo-DL-tryptophan and ethyl bromopyruvate; 1 H-NMR (CDC13): (5 10.41 (m, s), 7.80 (1H, d), 7.38 (1H, d) , 85585 • 167- 200307684 7.24 (1H, d), 7.18 (1H, dd), 6.06 (1H, s), 4.21 (4H, dd), 4.03 (1H, m), 3.68 (1H , D), 2.88 (H, dd), 1.24 (6H, m); MS (ESI) · 407, 409 (MH +). B. The title compound is similar to that described in Example 2A, 8-Bromo-1,2,3,6-tetrahydronitrogen is used to incorporate [4,5 hepta] indole-2,5-dicarboxylic acid diethyl ester (compound in Step 骡 A) and chlorinated 4 -Made of Fluorobenzine; 1 H-NMR (CDC13): 510.20 (1H, s), 8.20 (1H, s), 7.63 (2H, m), 7.41 (1H, d), 7. · 32 (1H, d), 7-13 (3H, m), 6.14 (1H, m), 4.12 (2H, m), 3.97 (1H, dd), 3.76 (1H, m), 2.98 (H, dd), 1.11 (3H, t), 0.68 (3H, t); MS (ESI): 529, 531 (MH +). C. In a manner similar to step B, but use as appropriate Rhenium chloride replaced 4-fluorobenzidine chloride to prepare the following compounds : 8 · bromo-3- (3-fluorobenzylidene) -1,2,3,6-tetrahydroazepine [4,5-b] indole-2,5-dicarboxylic acid diethyl Esters; MS (ESI): 529, 531 (MH +); 8-bromo-3 · (2-fluorobenzyl) -1,2,3,6-tetrahydronitrogen [4,5-b ] p5j diethyl-2,5-dicarboxylate; MS (ESI): 529, 531 (MH +); and 3-ethylammonyl-8-bromo-1,2,3,6 · tetracarbazine Breathing [4,5 hepta] oxindole-2,5 · diethyl dicarboxylate; MS (ESI): 449,451 (ΜΗ +). Example 28 1,2,3,6-tetrahydronitrogen is hydride [4 , 5_B] Preparation of indole_2,5_dipicanoic acid 5-ethyl ester

[1,2,3,6-Tetrahydronitrogenated [4,5 = Bb] indole-2,5-dicarboxylic acid diethyl ester (0.48 g, 1.46 mmol) in MeOH (6 ml To the suspension in), 4N LiOH water 85585 -168-200307684 solution (1 ml) was added, and the suspension was stirred at 20 ° C for 2 hours. The solvent was removed and the crude was dissolved in water (50 ml). The aqueous solution was then extracted with Et0Ac (3x30 mL) and acidified with HOAc. A precipitate appeared, which was collected by tritium, washed with water and EtOAc, and then dried under high vacuum to give the title compound (300 mg); 1H-NMR (MeOH-d4): 5 8 · 06 (1H, s) , 7.54 (1H, dd), 7.44 (1H, dd), 7.12 (2H, m), 4.43 (3H, m), 3.61 (1H, d), 3.41 (1H, m), 1.49 (3H , T); MS (ES): 301 (MH +). Example 29 2- (hexaazapyridin-1-yl) -1,2,3,6_tetrahydronitrogen fused 4,5-B], Preparation of 5 | Indole 5-Ethyl Acetate

[1,2,3,6-tetrahydronitro]-[4-, 5-hepta] indole-2,5-dicarboxylic acid 5-ethyl ester (45 mg, 0.15 mmol) in DCM (3 ml) To the suspension was added CDI (27 mg, 1.1 equivalents). After stirring at 20 ° C for 1 hour, hexahydropyridine (23 µl, 1.5 equivalents) was added. The mixture was stirred at 20 ° C overnight and a clear solution was obtained. The solvent was evaporated to obtain a crude product, which was purified by trituration with MeOH to obtain the title compound (22 mg); 1H-NMR (CDC13): d 10.44 (1H, br s), 7.95 (1H, d), 7.38 ( 2H, d), 7.05-7.13 (2H, m), 6.69 (1H, d), 4.29 (2H, q), 3_98 (1H, dd), 3.65-3.73 (2H, m), 3.46 (1H, m), 3.31 (1H, m), 2.71 (1H, dd), 1.58-1 · 76 (6H, m) 5 1.36 (3H, t); MS (ES): 368 (MH +) 85585 -169 -200307684 Example 30 2-ethylaminomethylamidino-3_ (4-fluorobenzylidene) -1,2,3,6-tetrahydroazepine- [4,5-8] &lt; indole-5 -Preparation of ethyl acid acid

A. 2-Ethylaminomethylamido-1,2,3,6-tetrahydronitrocarbazone [4,5-b] pyrene-5_carboxylic acid ethyl ester is used in a manner similar to that described in Example 29 It was purified by chromatography on silica gel with ethylamine and prepared by dissociation with EtOAc-hexane (1: 1). B. The title compound was used in a manner analogous to that described in Example 2A to utilize 2-ethylaminomethylamido-1,2,3,6-tetrahydronitrogen to entrain [4,5Hepta] indole-5-carboxyl. Made from ethyl acetate and 4-fluorobenzidine chloride; 1H-NMR (CDC13): δ 10.21 (lH, brs), 8.27 (lH, s), 7.71-7.79 (3H, m), 7.53 (1H, m), 7.36 (1H, d), 7.20 (1H, m), 7.11 (2H, m), 6.11 (1H, d), 5.32 (1H, t), 4.21 (2H, m), 3.87 (1H, dd), 3.20 (1H, dd), 2.86-3.06 (2H, m), U8 (3H, t) 5 0.57 (3H, t); MS (ES): 450 (MH +). Example 31 3- (4-Fluorobenzyl) -2- (4-fluorobenzyloxy) methyl-1,2,3,6-tetraargonium [4,5_Β], 51 indol-5-di Ethyl carboxylate and 2- (4-fluorobenzyloxy) methyl-1,2,3,6-tetrahydronitrocarba [4,5-BH 丨 indol-5-dicarboxylic acid ethyl ester preparation

31a 31b 85585 -170 200307684 Α · 2-Hydroxymethyl [1,2,3,6-tetrahydronitro] [4,5_b],? 5-Hydroxycarboxylic acid ethyl ester is similar to that described in Example 1A The method described above is made using 2-hydroxymethyltryptamine oxalate. B. The title compound was used in a manner similar to that described in Example 2A to use 2-hydroxymethyl-1,2,3,6-tetrahydronitrogen to indole [4,5-b] indole-5-carboxylic acid ethyl. Ester with 4-fluorobenzidine chloride; 31a: 1H-NMR (CDC13): 5 10.46 (1H, br s), 8.15 (1H, s), 7.97 (2H, m), 7 · 58 (2H, m), 7.53 (1H, d), 7.39 (1H, d), 7.06-7.24 (6H, m), 5.96 (1H, m), 4.12-31 (4H, m) , 3.73 (lH, dd), 3.17 (lH, dd), 1.20 (3H, t); MS (ES): 531 (MH +); 31b: 1H-NMR (CDC13): 5 10.42 (1H, br s), 8 · 14 (1H, s) 5 8 · 05 (2H, m), 7_81 (1H, d), 7.42 (1H, d) 5 7.34 (1H, m), 7.04_7 · 22 (3H, m ) 5 5.62 (1H, m), 4.45 (1H, dd), 4.25-4.35 (3H, m), 4.08 (1H, m), 3.25 (2H, m), 1_35 (3H, t); MS (ES) : 409 (MH +). Example 32 Preparation of 1 · methyl-1,2,3,6-tetrahydronitrazine [4,5-8], 5 丨 indol-5_carboxylic acid ethyl ester

A. To a stirred solution of 3-indolylacetonitrile (3.9 g, 25 mmol) in DCM (100 ml, anhydrous), add BOC anhydride (6.5 g, 30 mmol), DMAP ( 3.6 grams, 30 millimoles) and TEA (4.2 milliliters, 30 millimoles). After 2 hours, the reaction mixture was diluted with DCM (100 mL), washed with 1NHC1 (2 X 50 mL) and brine, then dried (Na2S04), concentrated, and chromatographed (silica gel, 6% EtOAc / hexane), Production of (1-tert-butoxycarbonylamidin-3-yl) acetonitrile (5.4 g, 84%) as a pale yellow solid; 1H-NMR (CDC13): (58.17 (lH, brd), 85585 • 171- 200307684 7.64 (1H, br s), 7.52 (1H, br d), 7.38 (1H, app t), 7.30 (1H, app t), 3.78 (2H, s), 1.68 (9H, s) B. Stirred solution in (1-tert-butoxycarbonylpyridin-3-yl) acetonitrile (5.30 g, 20.7 mmol) in THF (20 ml, anhydrous), quenched to _78 ° C Inside, a ΐ · Μ solution of UHMDS in THF (21 ml, 21 mmol) was added dropwise. After 40 minutes, methyl iodide (1.3 ml, 21 mmol) was quickly added and the reaction mixture was allowed to warm to Ambient temperature. After 15 hours, the reaction was quenched by adding 0.2NHC1 (100 mL) and extracted with Et20 (2x100 mL). The combined extracts were washed with brine, dried (Na2S04), concentrated, and chromatographed (Silicone, 6% EtOAc / Hexane) to obtain 2- (1-third-butoxycarbonylindole-3-yl) propionitrile (the title compound) (4.0 g, 71%) as a pale yellow oil; 1h_NMR (CDC13): 5 8.17 (1H, bi: d), 7.60 (2H, m), 7.37 (1H, br d), 7.30 (1H, app t), 4.10 (1H, q), 1.76 (3H, d), 1.68 (9H, s). C. In a stirred solution of 2- (1-tert-butoxycarbonylindol-3-yl) propionitrile (4.00 g, 14.8 mmol) in DCM (10 mL) TFA (10 mL) was carefully added. After 1 hour, the reaction was diluted with DCM (40 mL), washed with water (2x40 mL) and brine, then dried (Na2S04), and concentrated under reduced pressure, and 2- (1H-adol-3-yl) propionitrile (2.5 g, 99%) was obtained as a light brown solid; 1H-NMR (CDC13): δ 8.25 (1H, d), 7.69 (1H, s ), 7.65 (1H, d), 7.45 (1H, app t), 7.37 (1H, app t), 4.12 (1H, q), 1.79 (3H, d), D · Stir in LAH (3.4g, 90mmol) in THF (40ml, anhydrous), and then chill to 0 ° C: add the 2- (1Η-β 丨 vocal_3_yl) c to the suspension Nitrile (2.5 g '14.7 Amor) in THF (40 ml' anhydrous In the solution. The reaction mixture was allowed to warm to ambient temperature and then heated under reflux. After 1 hour, the reaction 85585 -172- 200307684 reaction mixture was cooled to 0 ° C and the reaction was carefully quenched with moist THF (5-10% H2 0) until gas evolution ceased. The resulting mixture was filtered through CeliteTM and concentrated to give a brown residue. Rinse the filter with Et20 (100 ml), combine it with the residue, dehydrate and dry (Na2S04), and concentrate under reduced pressure to produce 2_ (1Η-ρ5 丨 lar-3-yl) propylamine (2.1 g, 82 %), A light amber oil; 1H-NMR (CDC13): 5 8 · 28 (1H, br s), 7_61 (1H, d), 7.36 (1H, d), 7.16 (1H, app t), 7.08 (1H, app t), 6.96 (1H, br s) 5 3.41 (2H, br s), 3.19 (1H, q), 2.95 (2H, app d), 1.35 (3H, d) · E · In a manner similar to Example 1A, but using on-site 2- (lHW 丨 indol-3-yl) propanamine hydrochloride made from one equivalent of anhydrous HC1 / dioxolane to replace tryptamine hydrochloride, 1-Methyl-1,2,3,6-tetrahydronitropyrene [4,5 VII &gt;? 丨 indole-5-carboxylic acid ethyl ester as the title compound; MS〇ESI): 271 (MH +). F · In a manner similar to Example 2A, but using 1-methyl-1,2,3,6 · tetrahydronitrogeno [4,5Hepta] indole-5-carboxylic acid ethyl ester, replacing 1,2, 3,6_tetrahydronitrogen is fused with [4,5-bH 丨 indole-5-carboxylic acid ethyl ester to make 3- (4 · fluorobenzyl) small methyl 1,2,3,6-tetra Hydrogen and nitrogen enzymatically bind [4,5-b] indole-5 · chitoate; 1 H-NMR (CDC13): 510.54 (1H, br s), 7.97 (1H, s), 7 .63-7.68 (2H, m), 7.58 (1H, d), 7.39 (1H, d), 7.09-7 · 23 (4H, m) 5 5.28 (1H, dd), 4.25 (2H, m), 3.85 (1H, m), 3.18 (1H, d), 1.34 (3H, d), 1.22 (3H, t); MS (ESI): 393 (MH +). G · to Similar to the method described in step F, but replacing 4-fluorobenzyl chloride with appropriate thorium chloride, the following compounds were prepared: 3- (4-chlorobenzyl) small methyl +2,3,6 -Tetrahydronitrogeno [4,5 hepta] indole-5-carboxylic acid ethyl ester; 1 H-NMR (CDC13): 510.53 (1H, br s), 7.95 (1H, br s), 7.55-7.60 ( 3H, m), 7.46 (2H, d), 7.38 (1H, d), 7.21 (1H, app t), 7.12 (1H, app t), 5.26 (1H, 85585 -173- 200307684 dd), 4.25 (2H, m), 3.85 (1H, m), 3.18 (1H, d), 1.34 (3H, d), 1.22 (3H, t ); MS (ESI): 409 (MH +); 3_ (3,4_difluorobenzylidene) _i_methyltetrahydronitrogero [4,5hepta-5-carboxylic acid ethyl ester; MS (ESI): 411 (MH +); 3_ (4_p-methoxybenzyl) -1-methyl_i, 2,3,6-tetrahydronitrogen [4,5Hepta] pyridin-5 -Ethyl carboxylic acid; MS (ESI): 405 (MH +); and 3-Sunflower fluorenyl-1-methyl-1,2,3,6-tetrahydronitrogeno [4,5-b] ind Indole-5-carboxylic acid ethyl ester; MS (ESI): 419 (MH +) ·· Η · In a manner similar to that described in steps A to E, but in step β- (1-third-butoxycarbonylindole) During the alkylation of -3-yl) acetonitrile, 2 equivalents of methyl iodide were used to prepare the following compounds: U-dimethyl-1,2,3,6_tetrahydronitrogeno [4,5-b] ind Indole-5-carboxylic acid ethyl ester; MS (ESI): 285 (MH +). I · In a manner similar to that described in Example 2A, but using ι, ι_dimethyl 4,2,3,6-tetrahydro Nitrogen [4,5-b] indole-5-carboxylic acid ethyl ester, replacing ι, 2,3,6_tetrahydronitrogen benzo [4,5hepta] indole-5_carboxylic acid ethyl ester, The following compounds were prepared: 1,1-dimethyl_3- (4 • fluorobenzylidene) -1,2,3,6-tetrahydronitrogen [[, 5, b] 4] -Ethyl carboxylate; 1 H-NMR (DMSO-d6): 5 10.82 (1H, s), 7.76 (1H, d), 7.65 (1H, s), 7.61 (2H, dd), 7 · 54 (1H, d), 7.35 (2H, app t), 7.09 (1H, app t), 6.98 (1H, app t), 4.22 (2H, q), 3.97 (2H , Br s), 1_52 (6H, s) 5 U7 (3H, t); MS (ESI) · · 407 (MH +) · J. In a similar manner to step I, but using appropriately substituted benzyl chloride Thorium-substituted 4-fluorobenzyl chloride , The following compounds were prepared: 3- (4-chlorobenzyl) -1,1-dimethyl-1,2,3,6-tetrahydronitrogeno [4,5heptadium indole-5- Ethyl carboxylate; 1 H-NMR (DMSO-d6): (510 · 81 (1Η, s), 7.76 (1Η, d), 7.63 (1Η, 85585 -174- 200307684 s), 7.51- 7.61 (5H, m), 7.09 (1H, app t), 6_98 (1H, app t) 5 4.22 (2H, q), 3.96 (2H, br s), 1.52 (6H, s) , U8 (3H, t); MS (ESI): 423 (MH +); 3- (3,4_monomurinomethyl) _1,1_monomethyl-1,2,3,6_tetrahydro Nitrogen [4,5-bp? 丨 Homo-5-carboxylic acid ethyl ester; MS (ESI): 425 (MH +); 3- (4-p-methoxybenzylmethyl) _1,1_monomethyl -i, 2,3,6-tetrachloroazepine [4,5-b] p5 | ethyl indole-5-carboxylic acid; MS (ESI): 419 (MH +); and 1,1-dimethyl -3-Sunflower fluorenyl-1,2,3,6_tetrahydroazepine [4,5seven] pyrene-5-carboxylic acid ethyl ester; MS (ESI): 433 (MH +) · K. Similar The method described in steps 骡 A to E, but during the alkylation of (μ tertiary-butoxycarbonylindol-3-yl) acetonitrile in step 骡 b, use bromoethane to replace the formazan. Into the intermediate 1-ethyl-1,2,3,6-tetrachloroazepine π and [4,5-b] v5 丨 no-5-carboxylic acid ethyl ester. In a similar manner to Step 骡 F, but with [ethyl, 1,2,3,6-tetrahydronitro], [4,5-b] indole-5-carboxylic acid ethyl ester, replacing 1.methyl. ι, 2,3,6-tetrahydronitrogen is incorporation of [4,5seven] 4 indole-5-carboxylic acid ethyl ester to prepare the following compounds: 1-ethyl-3 · (4-fluorobenzyl) -1,2,3,6-tetrahydronitrocarbazone [4,5hepta] indole-5-carboxylic acid ethyl ester; 1H-NMR (DMSO-d6): 5 10.87 (1Η, s), 7.94 (1Η, s), 7.69 (2Η, m), 7.52 (2H, app t), 7.41 (2H, app t), 7.08 (1H, app t) 5 7.0 (1H, app t), 5.13 (1H, d), 4.20 (2H, m), 3.56 (1H, m) 5 3.08 (1H, d), 1.48 (1H, m), 1.14 (3H, t), 0.93 (3H, t); MS (ESI): 407 (MH +). L · In a manner similar to Step K, but replacing the 4-fluorobenzidine chloride with an appropriately substituted rhenium chloride, the following compounds were prepared ... 3 -(4-chlorobenzyl) small ethyl 1,2,3,6_tetrahydronitrogeno [4,5_b] indole-5-carboxylic acid ethyl ester; MS (ESI): 423 ( MH +); 3- (3,4-difluorobenzyl) small ethyl_1,2,3,6_tetrahydronitrogeno [4,5-b] indole-5- 85585 -175- 200307684 Ethyl methanoate; MS (ESI) · 425 (MH +); 1 (4-p-methoxybenzyl) Small ethyltetrahydronitrogero [4,5Hepta> 5 | ethyl indole-5-carboxylic acid; Ms (ESI): 419 (MH +); and 1-ethyl sunflower fluorenyl 1,2,3 , 6_tetrahydronitrocarba [4,5-b] p5 丨 Homo-5-carboxylic acid ethyl ester; MS (ESI): 433 (MH +) · Example 33 7 · (3,4 · Difluorobenzidine Group) _6,7_dihydro-5H-10-oxo-7-nitro-benzo [A] Preparation of ethyl blue olein-9_ carboxylic acid

A. Prepared in a manner similar to that described in steps C and D of Example 32, but replacing 2- (1-third-butoxycarbonylearm-3-yl) propionitrile with 3-benzofurylacetonitrile to make Intermediate 3-aminoethylbenzofuran; MS (ES): 162 (MH +) · B · In a manner similar to that described in Step 32 of Example 32, but replacing with 3-aminoethylbenzofuran 2- (lH-indole-3-yl) propylamine to make intermediate 7,7-difluorene_5Η_1〇ϋazepine [a] blue sesame oil_9_carboxylic acid ethyl ester; MS (ES): 258 (ΜΗ +). C. In a manner similar to that in Example 32, step F, but using the intermediate 6,7-difluorene-5H-10-oxo-7 · nitrobenzo [a] blue sesame oil_9_carboxylic acid Ethyl ester and 3,4-difluorobenzidine chloride were used to prepare the title compound; 1NMR (CDC13): 5 7.46-7.53 (4H, m), 7.34 (2H, m), 7.25 (2H, m), 4 · 33 (2H, q), 4.21 (2H, t), 3.17 (2H, t), 1.32 (3H, t) · MS (ES): 398 (MH +). D · In similar steps A to C method, but 3-benzopyranylacetonitrile was substituted for 3-benzopyranylacetonitrile in step VII with 3-benzopyrimidineacetonitrile to prepare the following compounds: 85585 -176- 200307684 7 · (3,4-difluorobenzyl)- 6,7-dihydro-5H-10-sulfur · 7 · nitrogen · benzo [a] blue Soot-9-carboxylic acid ethyl acetate; 1NMR (CDC13) ·· (5 8 · 15 (1H, s), 7.84 (1H, m), 7.67 (1H, m), 7.50 (1H, m) , 7.38 (3H, m), 7.30 (1H, m), 4.24-4 · 30 (3H, m), 3.34 (2H, t), 1.27 (3H, t). MS ( ES): 414 (MH +). Example 34 8-Ethoxy-3_ (4-fluorobenzyl) -l, l-dimethyl-1,2,3,6-tetrahydronitro ## [4 , 5-B] Preparation of ethyl indole-5-metanoate.

A. Decomposed methane (15 ml) was added to a stirred mixture of 6-oxooxycystamine (10 g, 35.66 mmol) in anhydrous benzene (15 ml) at ambient temperature. The mixture was stirred at ambient temperature for 30 minutes and then allowed to stand overnight in the dark. The solid was collected by filtration, and then dried under high vacuum to obtain (6 · benzyloxy-1H-indole-3-ylmethyl) trimethylammonium iodide (17.5 g). Β. (6-Benzyloxyindol-3-ylmethyl) trimethylammonium iodide (2.2 g, 5 * Mol), sodium cyanide (500 mg, 10.2 mmol) and 95 % EtOH (50 mL) / m compound, refluxed under nitrogen for 5 hours. The solvent was removed in vacuo and the residue was dissolved in DCM and washed with water, then dried over sodium sulfate and evaporated in vacuo to give a white solid which was recrystallized from EtoH to give Ethoxy-1H-fluorenyl | yl> acetonitrile (1.25 g, 86%). (ES): 263 (MH +). C. (6_Ethoxy-1H-indolyl) _acetonitrile was protected by di-tertiary dicarbonate (BOC20), using as in Example 32 Under the same conditions as described, &amp; 85585 -177- 200307684 'Gasylcyanomethyl 1 ^ 丨 Homo-1-butyric acid tert-butyl alcohol; MS (ES): 363 (MH +). Methyl 3-cyanomethyl-4-indol-1-acid third-butyl ester methylation was performed in a manner similar to that described in Example 32, Step B, but during the alkylation, Using 2 equivalents of methyl iodide to obtain 6-benzyloxycyano (dimethyl) methyl) P? 丨 indole-1-carboxylic acid tert-butyl ester; MS (ES): 391 (MH +). Ε · In a manner similar to that described in Step 32C of Example 32, 6-benzyloxy-3_ (cyano (dimethyl) methyl 丨 indole + carboxylic acid third-butyl ester was removed and protected to obtain 厶 (6_ 爷Oxy-1Η-indole_3 · yl) _2methylpropionitrile; MS (ES): 291 (ΜΗ +). F. In a manner similar to that described in Example 32, Step D, 2_ (6_ 芊 oxygen Reduction of 1-methyl-indol-3-yl) -2-methyl-propionitrile with LAH to give 2- (6-benzyloxy_1-indol-3-yl) -2-methyl-propylamine Hydrochloride; ms (ES): 295 (ΜΗ +). G. 芊The radical _U_dimethyl-1,2,3,6-tetrahydronitrogeno [4,5 七] 4 丨 indole-5_carboxylic acid ethyl ester is used in a manner similar to that described in Example 1A, using 2 -(6-benzyloxy-1H · loxa-3-yl) -2-methyl-propylamine hydrochloride. H. The title compound was prepared in a similar manner to that described in Example 2A using 4-chloride. Made from fluorobenzidine; MS (ES): 513 (MH +) I · In a similar manner to that described in step CH, but in step 骡 c, replace with 5-benzyloxyindole_3_acetonitrile (6 -Benzyloxy_1H-indol-3-yl) acetonitrile to prepare the following compound: 9- + oxy-3- (4-fluorobenzylfluorenyl) -fluorene, i-dimethyl_i, 2, 3,6-Tetrahydronitrogeno [4,5Hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 513 (MH +). Example 35 8-Difluorenylamino_3_ (4_fluoro Preparation of benzamidine) _1,1_dimethyl_1,2,3,6-tetrahydronitrogeno [4,5 · B], 5 | Indole-5-carboxylic acid ethyl ester 85585 • 178- 200307684 ο

Α. Add benzyl bromide (10 ml, 84.2 mmol) to (6-amino-l-I-pyrene-3_yl) acetonitrile (Brown, R.K .; Garrison at ambient temperature and nitrogen) , RA ·, · m. CAem · &amp; c · (1955), Vol. 77, pp. 3839-3842) (5.16 g, 30-14 mol), potassium carbonate (10.83 g, 78.36 mol) , A stirred mixture of sodium iodide (560 mg, 3.74 mmol) and anhydrous DMF (150 ml). The resulting mixture was stirred at ambient temperature overnight, then poured into a mixture of water and extracted with ethyl acetate. The combined extracts were washed with ammonium chloride solution and evaporated in vacuo. The residue was purified by chromatography on silica gel, and dissolved in hexane-ethyl acetate (85: 15) to obtain (6-dibenzylamino-1H-pyridin-3-yl) · acetonitrile (8.8 g). ; MS (ES): 352 (MH +). B. The title compound was replaced in a manner similar to that described in Example 34C-H, except that in step C, 'dibenzylamino_1Η-yl] Oxy-1Eμ indole-3-yl) acetonitrile; MS (ES): 602 (ΜΗ +). C · In a similar manner, but using (6-benzyl (methyl) amino-1H-ind Indole · 3-yl) acetonitrile or (5-amino-1Η-indol-3-yl) acetonitrile, replacing (6-amino-1Η-indol-3-yl) acetonitrile to prepare the following compounds: 8- ( (Methyl) amino) 4,1-dimethyl-1,2,3,6-tetrahydronitrocarba [4,5Hepta] indole-5-carboxylic acid ethyl ester; MS (ES) · 404 (ΜΗ +); and 9-dialkylamino-1,: ^ dimethyltetrahydronitrogen is used to incorporate [4,5-b] oxindole-5-carboxylic acid ethyl ester. D · In a manner similar to that described in step 2A, but using compound 85585 -179- 200307684 from step C in place of 1,2,3,6_tetrahydronitrogeno [4,5-b: N indol-5-carboxyl Acid ethyl ester, the following compounds are prepared: 8 · (Nyl (methyl) amino) -3- (4-fluorobenzyl) _1, 丨 -dimethyl-1,2,3,6-tetrahydro Nitrogen [4,5 hepta] indolin-5-carboxylic acid ethyl ester; MS (ES) · 526 (MH +), with 9-dibenzo [amino-3- (4-fluorobenzylhydrazine) ) -U · dimethyl-1,2,3,6-tetrahydronitrocarbazone [4,5 hepta] oxindole-5-carboxylic acid ethyl ester; MS (ESI): 602 (MH +) · E · to Similar to step 2A, but using the methyl group (methyl) amino) -1,1-dimethyl-1,2,3,6 · tetrahydronitrogeno [4,5-b] camphor-5 -Ethyl carboxylate and 3,4-difluorobenzyl chloride, to prepare the following compounds: 8- (Branyl (methyl) amino) -3 · (3,4-difluorobenzyl) · 1,1-Dimethyl-1,2,3,6-tetrahydronitrogeno [4,5-bH-indol-5-carboxylic acid ethyl ester. MS (ES): 544 (ΜΗ +) Example 36 10-Alkyl-3- (4-fluorobenzylidene) -1,2,3,6-tetrahydronitrogen azeo [4,5 # 呻Ethyl indole-5-acidate and 8-bromo 3_ (4-fluorobenzyl) -1-, 2,3,6_tetrahydronitrogen [4,5_1)], 5 indole-5-carboxy Preparation of ethyl acetate

Br

Ethyl 3- (4-fluorobenzyl) &gt; ι, 2,3,6-tetrahydroazepine [4,5 hepta] indole-5-acrylic acid ethyl ester (0.38 g, 1¾ mole) To the solution in carbon tetrachloride (10 ml) was added &amp; bromosuccinimide (0.28 g, 1.55 mmol) and diphenylhydrazone peroxide (10 mg). The mixture was heated under nitrogen. It was refluxed for 30 minutes. After cooling at 85585 -180- 200307684, the solids were removed by filtration and washed with carbon tetrachloride. The filtrate was concentrated to obtain the crude product, which was purified by chromatography on silica gel. Dissolved in MeOH-DCM (1 ·· 19) to obtain 36a (1.8 mg) and 36b · (6.6 mg): 36a iH-NMR (CDCI3): (510.58 (1H, s), 8.04 (1H, s), 7.62 (2H, m), 7_53 (1H, d), 7.37 (1H, d), 7.18 (3H, m), 4 · 24 (4H, m), 3.23 (2H, m), 1 · 23 (3H, t) MS (ES): 457 (MH +); 36b.l} l-mAR (COC \ 3): δ 10.81 (1H, s), 8.11 (1H, s), 7.62 (2H, m ), 7.31 (1H, m), 7.24 (1H, m), 7.18 (2H, m), 6.98 (1H, m), 4.25 (2H, q), 4.20 (2H, t ), 3.78 (2H, t), 1.23 (3H, t); MS (ES): 457 (MH +) · Example 37 8- -l_ methyl -1,2,3,6_ argon nitrogen four call group and prepared _3_ (4-methyl acyl-fluorophenyl) [[5-indole carboxylate 4,5_BH of

Α · In 3- (4-fluorobenzylidene) -1-methyl-1,2,3,6_tetrahydronitrogeno [4,5-b] 4 indole-5 ethyl carboxylate (Compound in Example 32F) (110 mg, 0.28 mmol) In a stirred solution in 6 ml of DCM, NBS (48 mg, 0.27 mmol) was added at ambient temperature. The reaction mixture was stirred at ambient temperature under N2 for 1.5 hours, and samples were monitored by LC_MS. The solution was concentrated and purified by flash chromatography on silica gel and dissolved with EtOAc-hexane (0-30%) to give the title compound (124 mg) as a yellow solid; iH-NMRCCDCIs). 5 10.54 (1H, s ), 7.98 (1H, d), 7.63 (2H, m), 7.50 (1H, d), 7.39 (1H, m), 7.16 (3H, m), 5.26 (1H , Dd), 4.22 (2H, m), 3.78 (1H, m), 3.12 (1H, m), 1.28 (3H, d), 1.18 (3H, t). MS (ESI): 471, 85585 -181- 200307684 473 (MH +). Β · In a similar manner, but using an excess of NBS, the following compounds were prepared: 8,10-dibromo-3- (4-fluorobenzyl) small methyl- 1,2,3,6-tetrahydronitrile calls for [4,5-b] oxindole-5-carboxylic acid ethyl ester; MS (ESI) · 550 (MH +) · C. Similar as in step 骡 A Method, but using 3- (4-fluorobenzyl) -1,1-dimethyl-1,2,3,6-tetrahydronitrogeno [4,5-b] 4 indole_ Ethyl 5-carboxylate, which replaces 3- (4-fluorobenzyl) -1 · methyl-1,2,3,6-tetrahydronitrogeno [4,5-b] ^ indole-5- Ethyl carboxylate, the following compounds were prepared: 8-bromo-3- (4-fluorobenzylfluorenyl) _1,1_dimethyl-1,2,3,6-tetrahydronitrogen [4,5 -b] ethyl indole-5_carboxylic acid 1 H-NMR (CDC13): 510.81 (1H, s), 7_95 (1H, s), 7.73 (3H, m) 5 7 · 65 (1H, d), 7.26 (3H, m), 4.36 (2H , Dd), 1.72 (6H, s), 1.31 (3H, t); MS (ESI): 485, 487 (MH +). Example 38 3- (4-fluorobenzyl) -8-nitro-1 Of 2,2,3,6-tetrahydronitrocarbazone [4,5-B] indole · 5-acetic acid ethyl ester

A. A solution of nitric acid (90%, 50 µl, 1 mmol) in acetic acid (3 ml) was added dropwise to 1,2,3,6 · tetrahydronitrogen at 10 ° C. A stirred solution of [4,5-b] oxindole-5-carboxylic acid ethyl ester (256 mg, 1 mmol) in acetic acid (5 ml). The mixture was allowed to warm to ambient temperature and stirred for an additional 1.5 hours, then poured into a mixture of ammonium hydroxide and ice, and extracted with DCM. The combined extracts were washed with brine, dried over sodium sulfate, and evaporated in vacuo. 85585 -182- 200307684 The crude product was purified by chromatography on silica gel and dissolved with hexane-EtOAc (75: 25) to obtain 8-nitro-1,2,3,6-tetrahydronitrogen [4, 57 #] Ethyl-5-carboxylate (25 mg); 1H-NMR (CDC13): 5 11 · 52 (1H, s), 8.78 (1H, d), 8.43 (1H, m), 7. · 92 (1H, d), 7.82 (1H, dd), 7.46 (1H, d), 4.24 (2H, q), 3.52 (2H, m), 3.07 (2H, m), 1 · 27 (3H, t); MS (ES): 301 (MH +). B. The title compound was prepared in a manner similar to that described in Example 2A, using 8-nitro-1,2,3,6. Benz [4,5-b] oxindole-5-carboxylic acid ethyl ester and 4-fluorobenzyl chloride; MS (ES): 424 (MH +). Example 39 3- (4-fluorobenzyl ) -8- (3-methoxyphenyl) · 1,2,3,6-tetrahydronitrogen is inferred [4,5-8b 5 丨 Preparation of 5-acrylic acid ethyl ester.

Α. In 8_molyl-3_ (4-fluorobenzylidene) -fluorene, 2,3,6-tetrahydronitrogen, [4,5-bH ethyl-5-carboxylic acid ethyl ester (in Example 36A Compounds) (70 mg, 0.15 mmol), 3-methoxyphenyldihydroxyborane (58 mg, 0.38 mmol), and (o-tolyl) 3p (24 mg, 0.077 To the stirred liquid in toluene / EtOH (2: uml), 0.55 ml of a 1M NaHC03 solution and Pd (OAc) 2 (7 mg) were added at ambient temperature. The reaction mixture was heated with milk and milk for 15 hours, and samples were monitored by LC-MS. The solution was diluted with DCM (10 mL) and washed with brine. The aqueous phase was extracted twice with DCM (10 mL); The combined organic phases were dried over Na2S04 and concentrated. The crude product was purified by flash chromatography 85585 -183- 200307684 and dissolved in EtOAc-hexane (0-30%) to give the title compound (68 mg) as a pale yellow solid; 1H-NMR (CDC13) : 5 10.76 (lH, s), 8.20 (lH, s), 7.78 (4H, m), 7.52 (2H, m), 7.42 (1H, d), 7.36 (3H, m), 7.04 (1H, m), 4.43 (4H, m), 4.05 (3H, s), 3.45 (2H, m), 1.39 (3H, t), MS (ESI), 485 (MH +). B. Similar Method, but using 3-furan dihydroxyborane or 4- (2-aminoethyl) -morpholine to replace 3-methoxyphenyldihydroxyborane to prepare the following compounds: 3- (4-fluorobenzoic acid ) -8-octane-3-yl-1,2,3,6-tetrahydronitrocarba [4,5 七] 4 丨 Ethyl-5-carboxylic acid ethyl ester; MS (ESI): 445 (MH + ); And Chun 3- (4-fluorobenzyl) -8- (2-morpholin plin-4-yl-ethylamino) -1,2,3,6-tetrahydronitroazine [4 , 5-b] indole-5-acrylic acid ethyl ester; MS (ESI): 507 C. In a similar manner to step 骡 A, but using 8-bromo-3_ (4-fluorobenzyl) -1 -Methyl-1,2,3,6-tetrahydronitrogeno [4,5-b] indole-5-chinoic acid ethyl ester, replacing 8 · bromo-3- (4-fluorobenzylhydrazine) ) 1,2,3,6-tetrahydronitrogens entrain [ 4,5-b] Homo-5-quinic acid ethyl ester to prepare the following compound: 3- (4-fluorobenzyl) -8- (3-methoxyphenyl) -1_methyl_ι, Ethyl 2,4,6-tetraargonium [4,5 hepta] indole-5-metanoate; 1H-NMR (CDC13): 510.52 (1H, s), 7.92 (1H, d), # 7 56 (4H, m), 7.29 (2H, m), 7.17 (1H, m), 7.11 (3H, m), 6.81 (1H, m), 5.22 (1H, dd) , 4.20 (2H, m), 3.81 (4H, m), 3.12 (1H, m), 1.28 (3H, d), U5 (3H, t); MS (ESI): 499 (MH +). D. In a manner similar to steps A and B, but using 8-bromodongsfluorobenzylidene) -1,1-monomethyl_2,3,6_tetranitrogen entrained [4,5 七&gt; 5 丨 Ethyl-5-carboxylic acid ethyl ester, replacing 8-bromo-3- (4-fluorobenzyl) -i, 2,3,6-tetrahydronitrogen [4,5Hepta] indene Ethyl-5-chinoic acid ethyl ester, the following compounds were prepared: 3- (4-fluorobenzyl) -8- (3-methoxyphenyl) ― 丨 dimethyldimethyl 2,3,6_tetrahydro Nitrogen 85585 -184-200307684 and [4,5-b; N indole-5-carboxylic acid ethyl ester; 1H-NMR (CDC13): 5 10.71 (1H, s), 7.85 (1H, d), 7 · 81 (1Η, s), 7.63 (3Η, m), 7.35 (2Η, m), 7.23 (1Η, m), 7.20 (1Η, m), 7.13 (2H, m), 6 .88 (1H, m), 4.26 (2H, dd), 3.89 (3H, s), 1.68 (6H, s), 1.23 (3H, t). MS (ESI): 513 (MH +); With 3- (4 • Chrysanthemum spp.Kifan-3_yl-1,1-dimethyl-1,2,3,6-tetranitrogen, it is [4,5-b] pyridine · 5_ Ethyl carboxylate; 1H-NMR (CDC13): 5 10.67 (1H, s), 7.81 (2H, m), 7.76 (1H, t), 7.63 (2H, m), 7.48 (2H, m), 7.23 (1H, m), 7.13 (2H, m), 6.76 (1H, m), 4.26 (2H, dd), 3.89 (3H, s), 1.62 (6H , S), 1.21 (3H, t). MS (ESI): 473 (MH +). Example 40 8- (3-methoxyphenyl) -1,2,3,6-tetrahydronitrogen [ 4,5-B], Preparation of 5-oxindole-5-carboxylic acid ethyl ester

Α · 1 (4-Morylbenzyl) _8- (3-methoxyphenyl) -1,2,3,6-tetrahydronitrogen is [4,5-b] W *, wood-5 -In a stirred solution of ethyl metaboate (48 mg, 0.10 mmol) in 2 ml of EtOH, 0.30 ml of the solution at ambient temperature was added. The reaction mixture was heated under reflux at 93 C for 3.5 hours under N2, and samples were monitored by LC-MS. This solution was diluted with DCM (10 mL) and washed with brine. The aqueous phase was extracted twice with DCM (10 liters). The combined organic phases were dried over anhydrous and concentrated. The crude product was purified on a silica gel by flash chromatography and dissolved in EtOAohexane (0-30%) to give the title compound (33 mg) as a yellow solid; 1 H-NMR (CDCI3): 510.46 (1H, S) , 7.73 (1H, d), 7 47 (m, office 85585 -185- 200307684 7.37 (1H, d), 7.26 (2H, m), 7.12 (1H, m), 7.00 (1H, m) , 6.79 (1H, m) 5 5.25 (1H, s), 4.21 (2H, m), 3.80 (3H, s), 3.55 (2H, m), 3.11 (2H, m), 1 · 26 (3H, t). MS (ESI): 363 (MH +) · B · In a similar manner, but using the compound of Step 39 in Example 骡 C and D 'to replace 3- (4-fluorobenzylidene) ) -8- (3-Methoxyphenyl) -1,2,3,6 · tetrahydronitrogen is incorporation of [4,5-b] indole-5 · carboxylic acid ethyl ester to prepare the following compound: 8- ( 3-ethoxyphenyl) -1-methyl-l, 2,3,6-tetrahydronitrocarba [4,5 七] 4 丨 Homo-5-acrylic acid ethyl ester; MS (ESI): 377 ( MH +); 8- (3 • methoxyphenyl) _1, l_dimethyl_1,2,3,6_tetrahydronitrogeno [4,5Hepta] indole-5_carboxylic acid ethyl ester; MS (ESI): 391 (MH +); and 8-furan-3-yl-l, l-dimethyl-1,2,3,6-tetrahydronitrogeno [4,5hepta] pyridin-5 -Ethyl carboxylate; MS (ESI): 351 (MH +). C. Similar The method of Example 2A, but using 8- (3 • methoxyphenyl) -1,2,3,6 · tetrahydronitrogen, and [4,5 hepta] indole-5-carboxylic acid ethyl ester, replacing fluorene, 2,3,6-Tetrahydronitrogenates [4,5-b] Ethyl-5-carboxylic acid ethyl ester and replaces 4-fluorobenzyl chloride with 3,4-difluorobenzyl chloride , The following compounds were prepared: 3- (3,4-difluorobenzyl) -8- (3-methoxyphenyl) -i, 2,3,6-tetrahydronitrogen [4,5-b ] Indole-5-carboxylic acid ethyl ester; MS (ESI) · 503 (MH +). D · In a manner similar to step C, but using 8_ (3_methoxyphenyl) methyl_1,2,3 , 6-Tetrahydronitrogen is engulfing [4,5-b] H 丨 Homo-5-benzamic acid, and it is substituted for 1 (3-methyloxophenyl) _1,2,3,6-tetrahydronitrone [4,5-b] Ethyl-5-carboxylic acid ethyl ester, the following compounds were prepared: 3- (3,4-difluorobenzyl) -8- (3-methoxyphenyl)-丨 _form Ethyl 4,2,3, tetrahydronitrocarbazone [4,5Hepta] indole-5-carboxylic acid ethyl ester; MS (ESI): 517 (MH +). E. In a similar manner to step C, but using 8- (3-methoxyphenyl) -hydrazine, dimethyl-dimethyl 85585 -186- 200307684 -1,2,3,6-tetrahydronitrogen is entrained [4,5-b] 巧 I-5- Ethyl methanoate, or 8-succin-3-yl_1,1-dimethyl_1,2,3,6-tetrahydronitrogen is eh [4,5Hepta] doline-5-carboxylic acid Ester, replacing 8- (3-methoxyphenyl) -1,2,3,6-tetrahydronitrogen with [4,5 hepta] &lt; ethyl indole-5-carboxylic acid to prepare the following compounds: 3 · (3,4-difluorobenzyl) -8- (3-methoxyphenyl) -1,1-dimethyl-1,2,3,6 · tetrahydronitrogeno [4,5_bH indole _5_ Carboxylic acid ethyl ester; MS (ESI): 531 (ΜΗ +); and 3- (3,4-difluorobenzyl) -8-octane-3-yl-1,1-dimethylformate 1,2,3,6-tetrahydronitrogen benzopine [4,5_b; N indole-5-carboxylic acid ethyl ester; MS (ESI): 491 (MH +) · Example 41 3- (4-fluorobenzene (Formamyl) -7 · Weiji 1,2,3,6-tetrahydronitrocarbazone [4,5-; 8] Preparation of indole-5- leptate ethyl ester.

C02Et lu h A. 7-benzyloxy-3- (4-fluorobenzylidene) -l, 2,3,6-tetracarbazine entrains [4,5-b] indole-5-carboxyl Mixture of ethyl acetate (82 mg, 0-17 mmol) with 10% Pd / C (82 mg) and 1,4 · cyclohexadiene (0.15 ml, 1.58 mmol) at 50 ° C Stir for 2 hours. The catalyst was filtered off and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silica gel and dissolved with hexane-EtOAc (85:15) to give the title compound as a yellow solid (42 mg, 62%); iH-NMRCCDClO: 5 10.56 (1H, s) , 8 · 0 (1H, s) 5 7 · 64-7 · 59 (2H, m), 7.20-7.11 (3H, m), 6.97-6.93 (1H, m), 6.61-6.55 (1H, m), 5_33 (1H, br s), 4.27_4.20 (4H, m), 3.26-3.23 (2H, m) 51.25 (3H, t); MS (ES): 395 (MH +). 85585 -187- 200307684 B. In a manner similar to that described in step A above, but using the undecyloxy group> (4-fluorobenzylfluorenyl) -1,2,3,6-tetrahydronitrocarba [4,5-b] fluorene Indole-5-carboxylic acid ethyl ester, which replaces 7-benzyloxy-3- (4-fluorobenzylidene) -1,2,3,6-tetrahydronitrogeno [4,5VII] pyridine_ 5-Ethyl carboxylic acid, the following compounds were prepared: 3- (4-fluorobenzyl) -10-hydroxy-1,2,3,6-tetracarbazine [4,5-b; H 丨Indole-5-carboxylic acid ethyl ester; MS (ES): 395 (MH +) · C. In a manner similar to that described in Step A above ', but using 8-neoxy-3- (4-fluorobenzidine Phenyl) 1,1 · dimethyl-1,2,3,6-tetrahydronitrogen is eh [4,5 hepta] indole-5-carboxylic acid ethyl ester, 9-fluorenyl-3- (4- Fluorobenzyl) 1,1-dimethyl-1,2 , 3,6-Tetrahydronitrogeno [4,5Hepta] indole-5-carboxylic acid ethyl ester, or 9 · dibenzylamino-3- (4-fluorobenzylhydrazine) _1,1_ di Methyl 1,2,3,6_tetrahydronitrogeno [4,5 hepta] oxindole-5-carboxylic acid ethyl ester, replacing 7-fluorenyloxy-3- (4-fluorobenzylfluorenyl) · 1,2,3,6-tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid ethyl ester to prepare the following compounds: 3- (4-fluorobenzyl) -8 · hydroxy -1,1-dimethyl-1,2,3,6-tetrahydronitrocarba [4,5-b] oxindole-5-carboxylic acid ethyl ester; 1 H-NMR (CDC13): δ 10.45 ( 1H, s), 7.72 (1H, s), 7.66- 7.59 (3Η, m), 7.15-7.10 (2Η, m), 6.81 (1Η, d), 6.66 (1Η, dd), 4 · 84 (1Η, s), 4.24 (2H, q), 4.08 (2H, br s), 1.59 (6H, s), 1.24 (3H, t); MS (ES): 423 (MH +); 3- (4-fluorobenzylidene) -9-hydroxy-1,1-dimethyl-1,2,3,6-tetraazapine benzo [4,5-b] indole-5-carboxy Ethyl Ester; MS (ES) · 423 (MH +); and 9-fluorenylamino-3- (4-fluorobenzylfluorenyl) -l, l-dimethyl · 1,2,3,6-tetra Hydrogen-nitrogen is [4,5-b] oxindole-5-carboxylic acid ethyl ester; MS (ESI): 512 (MH +). Example 42 3_ (4_fluorobenzyl) -7-methoxy_ 1,2,3,6_tetrahydronitrogens [4,5-8], 5 丨 indole- Preparation of ethyl 5-acrylic acid 85585 -188- 200307684 ο

Α · 3- (4-fluorobenzylidene) -7-acyl-1,2,3,6_tetrahydronitrogen is inducing [4,5-b] W ethyl-5-carboxylic acid ethyl ester ( 65 mg, 0.16 mmol, potassium carbonate (54 mg, 0.39 mmol), decomposed methane (0.4 ml, 6.4 mmol) and anhydrous acetone (5 ml) at 60 ° C Stir for 13 hours. The potassium carbonate solid was filtered off, and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silica gel and dissolved in hexane_EtAc (90:10) to give the title compound as a yellow solid (36 mg, 55%); 1H-NMR (CDC13): δ 10.56 (1Η) , s), 7.98 (1H, s), 7.64-7.59 (2H, m), 7.18- 7.12 (3H, m) 5 7.03 (1H, t), 6.64 (1H, d), 4.28-4.19 (4H, m ), 3.96 (3H, s), 3.26-3 · 24 (2H, m), 1.24 (3H, t); MS (ES): 409 (MH +). B · In a similar manner, but using 3- (4- Fluorobenzyl) -i〇_Hydroxy-i, 2,3,6-tetrahydronitrobenzyl [4,5_b] indole-5-carboxylic acid ethyl ester, replacing 3- (4-fluorobenzidine Group) -7-hydroxy-1,2,3,6-tetrahydronitrogena [4,5-b; Hindol-5-carboxylic acid ethyl ester to prepare the following compound: 3- (4-fluorobenzyl (Methenyl) -10-methoxy-i, 2,3,6-tetrahydronitrocarbazone [4,5 hepta] oxindole-5-carboxylic acid ethyl ester; MS (ES): 409 (MH +). C. In a manner similar to that described in step IXA, except that 4- (2-chloroethyl) morpholine hydrochloride was used to replace the methyl iodide, the following compound was prepared: 3- (4-fluorophenylfluorenyl) -7- (2-morpholinolin-4-yl-ethoxy) -i, 2,3,6-tetrahydronitrogeno [4,5_b] indomo-5-acrylic acid ethyl ester; MS (ES ): 508 (MH +). Example 43 3- (4-fluorobenzyl Yl) winter (2_morpholine_4_yl-ethoxy) _1,2,3,6_tetrahydronitrazine 85585 -189- 200307684 [4,5-bh 丨 indole-5-carboxylic acid ethyl Preparation of 3_ (4_fluorobenzyl), hydrazone, fluorbenzyloxy) _1,2,3,6-tetrahydroazepine [4, ^ bh 丨 indole &amp; ethyl methanoate

A. 9 · Hydroxy-U, 3,6-tetrahydronitrogen is incorporated with [4,5 hepta] indole-5 · carboxylic acid ethyl ester (109 g, 0.4 mmol), potassium carbonate (28 mg, 20 mmol), sodium iodide 克 * g '0.4 mmol) and 4- (2-chloroethyl) morpholine hydrochloride (224 mg, h2 mmol) The mixture in anhydrous acetone (10 ml) was stirred at 800 c for 5 days. The solid was filtered, and the filtrate was concentrated in vacuo, then dried in high vacuum for several hours and used in the next reaction without further purification; MS (ES): 386 (MH +). Β · Make the crude product above It was dissolved in anhydrous DCM (15 ml) and triethylamine (0.9 ml) was added at 0 ° C, followed by 4-fluorobenzidine chloride (0.3 ml). The resulting mixture was stirred at ambient temperature overnight. The solvent was removed in vacuo and the residue was purified by chromatography on silica gel and dissolved in DCM-50% MeOH / DCM (80: 20) to give the title compound 43a (52 mg) and 43b (26 mg); 43a 1H-NMR (CDC13): 5 10.43 (1H, s), 7.97 (1H, s), 7.64-7.60 (2H, m), 7.27 (1H, m), 7.19-7.09 (2H, m ), 6.95 (lH, d), 6.88 (lH, dd), 4.28-4.17 (6H, m), 3.78-3.69 (5H, m), 3.22-3.20 (2H, m), 2.84 (2H, m), 2.66-2.51 (4H, m), 1.24 (3H, t); MS (ES): 506 (MH +); 43b, 1H-NMR (DMSO-d6): 5 11.00 (1H, s), 8.24-8.20 (2H , M), 8.05-7.99 (1H, m), 7.72_7.68 (2H, m), 7.59 (1H, d), 7.47-7.30 (5H, 85585 -190- 200307684 m), 6.97 (1H, d), 4.23 (2H, q), 4.07-4.02 (2H, m), 3.18 (2H, m), 1_20 (3H, t); MS (ES): 517 (MH +). C. In a similar manner, but replacing 1- (2-chloroethyl) hexahydropyridine hydrochloride with 4- (2-chloroethyl) morpholine hydrochloride, the following compounds were prepared: 3- (4-fluoro Benzamidine) -9- (2-hexahydropyridin-1-ylethoxy) -1,2,3,6-tetrahydronitrogeno [4,5-b] W indole-5-carboxylic acid Ethyl acetate; MS (ES): 5 06 (MH +). Example 44 8-Dimethylamine formamyloxy-3- (4-fluorobenzylidene) -1,1-dimethyl-1,23,6-tetrahydronitrogen [Preparation of ethyl 4,5-BHl indole-5-carboxylic acid

A · Dimethylamine formamidine chloride (0.2 ml, 2.17 mmol) is added dropwise to 3- (4-fluorobenzyl) -8-hydroxy-1 at 0 ° C under nitrogen, 1-Dimethyl · 1,2,3,6-tetrahydronitrocarbazone [4,5-b] indole-5-carboxylic acid ethyl ester (199 mg, 0.47 mmol), 4-dimethylamine Pyridine (DMAP) (20 mg) and triethylamine (0.8 ml, 5.74 mmol) in a stirred solution in anhydrous DCM (15 ml) and the resulting mixture was stirred at 50 ° C. for 5 hour. The solvent was removed in vacuo, and the residue was purified by chromatography on silica gel and dissolved in DCM-20% MeOH / DCM (90:10) to give the title compound (171 mg, 74%); 1H-NMR ( CDC13) ... (5 10.62 (1H, s), 7.78 (s, 1H), 7.74 (1H, d), 7.63-7 · 59 (2H, m), 7.16-7.10 (3H, m), 6.84 (1H, dd), 4.24 (2H, q), 4.08 (2H, br s), 3.14 (3H, s), 3.03 (3H, s), 1.59 (6H, s ), 1.23 (3H, t); MS (ES): 494 (MH +). 200307684 B. In a similar manner, but replacing the dimethylamine chloride with a suitable amine chloride or chloroformate Rhenium, the following compounds were prepared: 8-diethylaminemethylamidooxy, each fluorobenzyloxymethyl dimethyl, tetrachloronitrogeno [4,1 2 3 4 5 heptadol-5_carboxylic acid Ethyl ester; MS (ES): 522 (ΜΗ +); 3_ (4 • fluorobenzyl)> 4 ^ dimethyl_oxo (morpholine carbonylcarbonyloxy) 4,2,3, tetrahydro Nitrogen ', [4,5 hepta-5d-carboxylic acid ethyl ester; MS (ES) · 536 (ΜΗ +); H4-fluorobenzyl chloride 丄 dimethyl each (hexahydropyridine small carbonyl group (Oxy) _ 丨, 2,3,6_ Tetrahydronitrogen indeno [4,5Hepta] indole-5_carboxylic acid ethyl ester; MS (ES): 534 (M H +); 3- (4-fluorobenzylidene dimethyl-8_ (tetrahydropyrrole small carbonyloxy% tetrahydronitrogeno [4,5VII &gt; 5 indole-5_carboxylic acid ethyl ester; MS (ES): 520 (MH +); 8-diisopropylaminemethylamidooxy-3- (4-fluorobenzylidenedimethyltetrahydronitrogeno [4,5_b] indole_5 _Ethyl carboxylate; MS (ES): 550 (ΜΗ +); 3 · (4-fluorobenzyl dimethyl keto · tetrahydroimidazole small carbonyloxy) · 1,2,3,6 -Tetrahydronitrogenates [4,5_bH indole-5-carboxylic acid ethyl ester; MS (ES): 535 (MH +); 3- (Drylofluorobenzylhydrazone, μdimethylmethyl-phenyl- Carbamidyloxy-192- 1 2,3,6-tetrahydronitrocarbazone [4,5-bH indole-5-carboxylic acid ethyl ester; MS (ES): 556 (ΜΗ +); 2 3- (4-fluorobenzylfluorenylpyrene, μ dimethyl benzamidine methyl_hexahydropyridine__ 丨 _carbonyloxy) _1,2,3,6-tetrahydronitrogen [4,5 七] 4 丨 Indole-5_carboxylic acid ethyl alcohol; MS (ES) ·· 549 (ΜΗ +); 3 8-ethoxycarbonyloxy-3- (4-fluorobenzylfluorenyl) -pyrene, dimethyl Benzene_ι, 2,3,6_tetrahydronitrogero [4,5,5,5 indole-5_carboxylic acid ethyl ester; MS (ES): 495 (ΜΗ +); 4 3- (4-Gabenzene Formamyldimethyl phenoxycarbonyloxytetrahydronitrogen [4,5-bH 丨 indol_5_carboxylic acid ethyl ester; ms (ES): 543 (MH +); 8-fluorenyloxycarbonyloxy_3_ (4-fluorobenzylfluorenyl) -1,1_dimethyl-; ι, 2,3,6-tetrahydronitrogen [4,5_b] Ethyl indole-5-carboxylic acid; MS (ES): 557 (MH +); 5 85585 200307684 8-Ethyloxy-3- (4-fluorobenzylidene) -l, l-dimethyl_丨, 2,3,6-tetrahydronitrogen benzo [4,5H &gt;? 丨 Indole-5-carboxylic acid ethyl ester; MS (ES): 465 (MH +); and 8- (ethyl-isopropyl -Aminomethylamino) -3- (4-fluorobenzylidene) _ι, ι_dimethyl_1,2,3,6_tetrahydronitrogero [4,5-bH -5_ethyl citrate; MS (ES): 536 (MH +) · C. In a manner similar to that described in step 骡 A above, but using 3- (4-like benzamidine) -9- -1,1 · Dimethyl-1,2,3,6-tetrahydronitrogen deuterates [4,5Hepta] 啕 p-5-5-acrylic acid ethyl ester, replacing 3- (4-fluorobenzidine) ) -8-Hydroxy-1,1-dimethyl · ι, 2,3,6-tetrahydronitrogen is entrained with [4,5-b] Hou-5_acrylic acid ethyl ester, and 1 -Tetrahydror pilocarbamidine replaced dimethylformamide chloride to prepare the following compounds: 3- (4-fluorobenzyl) -1,1-dimethyldong (tetrahydropyrrole small carbonyloxy) ) 4,2,3,6-Tetrahydronitrogeno [4,5Hepta] indole-5_carboxylic acid ethyl ester; MS (ES): 520 (MH +). D. In a manner similar to that described in step C, but using 4-morpholine chloride or dimethyl chloroformate to replace 1-tetrahydro? Bilocarbonic acid chloride, the following compounds were prepared: 3 · (4_ Fluorenylmethyl) -1,1-monomethyl-9- (morpholin-1-weilyloxy) -1,2,3,6_tetrahydronitrogeno [4,5-bH indole _5_ Ethyl carboxylate; MS (ES): 536 (ΜΗ +); and 9-dimethylamine formamyloxy-3- (4-fluorobenzyl) -1,1_dimethyl -I, 2,3,6-tetrahydronitrocarbazone [4,5_b] oxindole-5_carboxylic acid ethyl ester; MS (ES): 494 (MH +) · E · In a similar manner to step A, However, 9-amino-1,1-dimethyl · 1,2,3,6-tetrahydronitrogen is used to entrain [4,5 hepta] indole-5-carboxylic acid ethyl ester to replace 3- (4- Fluorobenzyl) -8-Imino-1,1-difluorenyl · 1,2,3,6-tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid ethyl ester, The dimethylformamide chloride was replaced with methoxyacetamidine chloride to prepare the following compounds: 9- (2-methoxy-acetamido) -3 · (4-fluorobenzyl)- 1,1_Dimethyl-i, 2,3,6-tetra85585 -193- 200307684 Hydrogen-nitrogen [4,5Hepta] indole-5_carboxylic acid ethyl ester; MS (ESI): 494 (MH + ). F · In a manner similar to step E, but using Appropriate hydrazone chloride or monomethylammonium chloride was substituted for methoxyacetamidine chloride to prepare the following compounds: 9-Ethylamino-3- (4-fluorophenylamidinoyij-dimethyltetrahydronitropyrene [ 4,5 hepta] oxindole-5-carboxylic acid ethyl ester; MS (ESI): 464 (MH +); 3- (4-fluorobenzylamino) -9- (4-fluorobenzylamino) -l, l-dimethyl_1,2,3,6_tetrahydronitropyrene [4,5-b; H 丨 indol-5-carboxylic acid ethyl ester; MS (ESI): 544 (MH +); 9- (3,3-dimethyl-ureido) _3_ (4-fluorobenzylidene) -1,1 · dimethyl-1,2,3,6-tetrachloronitropyrene [4,5 7) Ethyl indole-5-carboxylic acid; MS (ESI): 493 (MH +) · G · In a manner similar to Step A, but using 9-fluorenylamino-1,1-dimethyl · 1,2 , 3,6-Tetrahydronitrogeno [4,5-b] Kl-Homo-5-acrylic acid ethyl ester, replacing 3- (4-fluorobenzylidene) ascites-1,1-dimethyl -l, 2,3,6-tetrahydronitrogen benzo [4,5-bH 丨 indole-5-carboxylic acid ethyl alcohol, to prepare the following compounds: 9- (1-benzyl-3,3-dimethyl- Urea) -3- (4-fluorobenzylidene) -1,1-dimethyl_i, 2,3,6-tetrahydroazepine [4,5-b] pyridin-5-carboxy Ethyl acetate; MS (ESI): 583 (MH +). Example 45 8_ (3,3_monomethyl-imidyl) -3- (4-fluorobenzyl) -1,1_dimethyl- i 2,3,6-Tetrahydronitrogeno [4,5-B] indole-5-acrylic acid ethyl ester and 3- (4-fluorobenzyl) -1,1-dimethyl-8- ( Preparation of trimethyl-ureido) 1,2,3,6_tetrahydronitrozine [4,5-BH indol-5_carboxylic acid ethyl ester

45a 45b 85585 -194- 200307684 A. Using the same conditions as described in Example 41, the compound of Example 35 was debenzylated to give 8-amino-3- (4-fluorobenzylidene) -1 , 1-Dimethyl-1,2,3,6-tetrahydronitrogeno [4,5H &gt;? Indol-5-carboxylic acid ethyl ester with 8-methylamino-3- (4-fluoro A benzamidine group) -U-dimethyl-1,2,3,6-tetrahydronitrazol [4,5 hepta] indole-5-carboxylic acid ethyl ester (about 1: 1) mixture. The mixture was used in the next reaction 'without further purification. B. The title compound was prepared in a manner similar to that described in Example 44, using 8-amino-3_ (4-fluorobenzylidene) -1,1-dimethyl-1,2,3,6_ Tetrahydronitrogero [4,5Hepta] indole-5_carboxylic acid ethyl ester and 8-methylamino-3- (4-fluorobenzylfluorenyl) _1,1_dimethyl-1,2, Made from a mixture of 3,6-tetrahydronitrobenzyl [4,5-b] indole-5-carboxylic acid ethyl ester; 45a: MS (ES): 493 (MH +); 45b: MS (ES): 507 (MH +) · Example 46 3- (4 • fluorobenzylidene) _1,1_dimethyl-8_ (trimethyladenosyl) -13,3,6-tetraargonium hydride [4,5_BH indole _5_ Ethyl methanoate and 8-[(2_Ga-ethyl) _methyl-amino-3- (4-fluorobenzyl) -1,1-dimethyl-1,2, Preparation of 3,6-tetrahydronitrogero [4,5-ΒΗ 1 indole-5-acrylic acid ethyl ester

46a 46b A. In a manner similar to that described in Example 41, 8- (benzyl (methyl) amino) -3- (4-fluorobenzylidene) _1,1-dimethyl-1,2 , 3,6-Tetrahydronitrogero [4,5-b] indole-5 · carboxylic acid ethyl ester is dephosphorylated to obtain 8-methylamino-3- (4-fluorobenzyl)- 1,1-dimethyl-1,2,3,6-tetrahydronitrocarba [4,5 hepta] indole-5-carboxylic acid ethyl ester; MS (ES) ·· 436 (MH +). B. In a manner similar to that described in Example 44, 8-methylamino-3- (4-fluorobenzyl 85585 -195- 200307684 amidinodimethyl-1,2,3,6-tetrahydronitrogen was engulfed [ 4,5-7] 4 丨 Ethyl indole-5-carboxylic acid is reacted with vaporized dimethylamine formamidine, and 1,2-dichloroethane is used instead of DCM as a solvent to obtain 3- (4-fluorobenzidine Dimethyl-8_ (trimethylureidotetrahydronitrogeno [4,5Hepta> 5 丨 indole-5-carboxylic acid ethyl ester. At the same time, 8 _ [(2_chloroethyl) methylamine [] Yl] -3- (4-fluorobenzylfluorenyl), ι, ι_dimethylxin, 2,3, tetrahydroazepine [4,5 hepta] oxindole-5-carboxylic acid ethyl ester, as Fewer by-products; MS (ES): 498 (MH +) · C. In a manner similar to that described in steps A and B, but in step b, 8- (benzyl (methyl) amino) -3 is used -(3,4_difluorobenzyl Dimethyl · m-tetrahydronitrogeno [4,5 ?? Indole-5-renylacetate, replacing 8 (benzyl (methyl) amino) _3_ (4_fluorobenzyl)- 1,1-Dimethyl · 1,2,3,6-tetrahydronitrogen is entrained with [4,5Hepta] indole-5_carboxylic acid acetamidine and substituted with lactoform for 1,2-one murine. , The following compounds were prepared: 3- (3,4_difluorobenzylhydrazine) _1,1_dimethyl_8_ (trimethylureidofluorene, 2, tetrahydronitrogen incorporation [4,5-bH丨 Ethyl_5_carboxylic acid ethyl ester. D * In a manner similar to that described in step C, but using chlorotetrahydropyrrolocarboxamidine or morpholine carbamonium chloride, replacing dimethylamine chloride Formazan, the following compounds are prepared: 3-4 fluorobenzyl dimethyl dimethyl each [methyl (tetrahydropyrrolocarbonyl) amino] _1,2,3,6-tetrahydronitrogen [4,5 -b] ethyl indole-5_chinoic acid; MS (ES): 533 (MH +); and 3- (4-fluorobenzyl) -1,1_dimethyl_8_ [methyl (? Fluoroline carbonyl) amine group] _U, 3,6-tetrahydroazepine [4,5Hepta] indole-5_carboxylic acid ethyl ester; MS (ES) ·· 549 (MH +). Example 47 8_ (2_dimethylamino_ethylaminomethylamidoxy) _3- (4-fluorobenzylmethyl) _ι, ι_dimethyl_1,2,3,6_tetrahydronitrogen [ 4,5 · Β] Preparation of indole 5-5-acrylic acid ethyl alcohol 85585 -196- 200307684

Α · Add triphosgene (58 mg, 0195 mmol) to 3 (4-fluorobenzylmethyl) groups at 0 ° C and Ν2, dimethyl, 2, 3, 4 Ethyl-6-tetrahydronitropyredo-5-carboxylate (49 mg, 0.116 mmol) and diisopropylethylamine (0.8 ml, 4.01 ¾ mole) in anhydrous DCM (1. Ml) of the stirred solution. The resulting mixture was stirred at ambient temperature for 15 hours, and N, N-diamidinoethylenediamine (0.1 ml, 0.9 μm mol) was added. The mixture was stirred at ambient temperature overnight. The solvent was removed in vacuo and the residue was purified by preparative reverse-phase HPLC to give the title compound (18 mg); 1063 (1H, s), 7.76 (2H, m), 7.63- 7.60 (2H, m), 7.16_7.11 (3H, m), 6.88-6.86 (1H, dd), 5.61 (1H, t), 4.24 (2H, q), 4.10 (2H , Br s), 3.37 (2H, m), 2.48 (2H, m), 2.27 (6H, s), 1.59 (6H, s), 1.24 (3H, t); MS (ES) ··· 537 (MH +). B · In a similar manner, but replacing N, N-dimethylethylenediamine with an appropriately substituted alcohol or amine, the following compounds were prepared: 8- (2--methylaminoethoxylactamyloxy (I group) -3- (4-Acetobenzyl) -1,1 · diT group_1,2,3,6-tetrahydronitrogen is indeno [4,5hepta] indole-5_carboxylic acid Ethyl ester; MS (ES) · 538 (MH +); 3- (4-fluorophenylfluorenyl) -l, l-dimethyl-8- (2-pyridin-2-yl-ethylamine) Alkoxy) -1,2,3,6-tetrahydronitrocarbazone [4,5indol-5-carboxylic acid ethyl ester; MS (ES): 538 (MH +); 3- (4-fluorobenzyl Fluorenyl) -1,1-dimethyl · 8- (pyridin-4-yl-methylaminomethylmethyloxy) _1,2,3,6_tetrahydronitrogen [4,5thindol- Ethyl 5-carboxylic acid; MS (ES): 557 (ΜΗ +); 3- (4-fluorobenzyl) -1,1- Methyl-8- (pyridin-2-yl-methylaminomethylamidoxy) 85585 -197- 200307684) 1,2,3,6_tetrahydronitrogeno [4,5-b] Kindole Ethyl-5-carboxylic acid; MS (ES): 557 (MH +); 8-Cyclopropylaminomethylamidooxy-3- (4 · fluorobenzylidene) -l, l-dimethyl · 1,2,3,6-tetrahydronitrocarbazone [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES) ·· 506 (ΜΗ +); 3- (4-fluorobenzyl) Fluorenyl) -1,1-dimethyl-8- (4-pyridine_2_yl-hexahydropyridine-1_carbonyloxy) · 1,2,3,6-tetrahydronitrogen hydride [4 , 5_b; Ethyl 5-N-carboxylic acid; MS (ES): 557 (MH +); 3- (4-fluorobenzyl) -l, l-dimethyl-8 Methyl-methylamine methyl ethoxy) -1,2,3,6-tetrahydronitrogen deuterates [4,5 七] acanth-5-acrylic acid ethyl ester; MS (ES): 557 (MH +) ; φ 8 _ (-nitrotetrafluorene small carbonyloxy) -3- (4-fluorobenzylidene) _1,1-dimethyl-1,2,3,6-tetrahydronitrogen is benzo [4,5 -b] ethyl indole-5-carboxylic acid; MS (ES): 506 (ΜΗ +); 3- (4-Acetomethyl) -1,1_dimethyl-8- (4-methyl Out of the hole nitrogen b Sakai-1-ylamine methylamino oxy) 1,2,3,6_tetrahydronitrogeno [4,5-bH 丨 indole-5-carboxylic acid ethyl ester; MS (ES) : 564 (MH +); 3 · (4-fluorobenzylidene)-醯, ι_ 二Methyl_8_phenethylaminemethylamidooxy- ^ tetrahydronitrogeno [4,5Hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 570 (MH +); 3- (4 • Fluorobenzyl) -14-dimethylheptaphene: methylmethylaminomethylammonyloxy ginseng 1,2,3,6-tetrahydronitrogen [4,5-b] Indole-5-carboxylic acid ethyl ester; MS (ES) · 557 (MH +); 3- (4-fluorobenzyl) -1, l-dimethyl-8- (sweet-2-ylmethyl Carboxamidooxy) -1,2,3,6, hydrogen and nitrogen [4,5_b] W Ethyl-5-carboxylic acid ethyl ester; MS (ES): 546 (MH +); Cyclobutylamine Fluorenyloxy_3- (4-fluorobenzylfluorenyl) -fluorene, ι · dimethyl-i, 2,3,6-tetrahydronitrogeno [4,5 七] indole_5_carboxy Ethyl Ester; (ES): 520 (MH +); 8-Cyclopentylaminomethylamidooxy-3- (4-fluorobenzylamido) -1,1-dimethyl-1,2,3 , 6-Tetrahydroazepine [4,5Hepta] indole-5-carboxylic acid ethyl ester; (Es): 534 (MH +); Cyclohexylaminocarboxyoxy-3- (4-fluorobenzyl) ) · Ι, ι · dimethyl ^ 2,3,6-tetra85585 • 198- 200307684 Hydrogen-nitrogen [4,5Hepta] eardoline-5-carboxylic acid ethyl ester; MS (ES): 548 (MH + ); 3 · (4 · fluorobenzylidene) -l, l-dimethyl-8- (5-methylpyridin-2-ylmethylamine formamyloxy) -1,2,3 , 6- Tetrahydronitrogenates [4,5 hepta] indole-5-carboxylic acid ethyl ester;] ^ (£ 3) ·· 572 (MH +); 3- (4-fluorobenzyl) -1,1 · Dimethyl · 8 · isopropylaminomethylammonyloxy-1,2,3,6-tetrahydronitrocarba [4,5hepta] oxindole-5-carboxylic acid ethyl ester; MS (ES): 508 (ΜΗ +); 3- (4-fluorobenzylidene) -1,1-dimethylaspartylaminomethylamidooxy-1,2,3,6-tetrahydronitrogen [4, 5 七] Adolyl-5 · carboxylic acid ethyl ester; MS (ES): 481 (MH +); 8_ (3_cyclopropyl-1 · methylureido) -3_ (4-fluorobenzyl) _1,1_dimethyl-1,2,3,6 · tetrahydronitropyrene [4,5_bHdol-5_carboxylic acid ethyl ester; MS (ES) ·· 519 (ΜΗ +); 8- (4 -Fluorobenzylmethylamino) -3- (4-fluorobenzyl) -l, l-dimethyl-1,2,3,6-tetrahydronitrogeno [4,5_bH 丨 indole _5_ Ethyl carboxylic acid; MS (ES): 558 (MH +); 3- (4-fluorobenzyl) -1,1-dimethyl-8- (1-methyl-3 · pyridine- 2-Methylmethylureido) -1,2,3,6-tetrahydronitrocarba [4,5-b] indole-5_carboxylic acid ethyl ester; MS (ES): 570 (MH +); 3 -(4-fluorobenzylidene) -1,1-dimethyl · 8 · (1-methyl-3-pyridin-2-yl-ethylureido) -1,2,3,6-tetra Hydrogen and nitrogen acyl [4,5_b; H 丨 indole-5 · carboxylic acid ethyl ester; _ 3- (4-fluorobenzene Fluorenyl) -1,1-dimethyl-9- (pyridin-2-yl-methylaminemethylamidinooxy) -1,2,3,6-tetrahydroazepine [4,5- b] Indyl-5-carboxylic acid ethyl ester; 3- (4 · fluorobenzyl) -1,1 · dimethyl-9- (2-pyridin-2-yl-ethylamine formamyloxy Radical) 1,2,3,6_tetrahydronitrogeno [4,5hepta] indole-5-acrylic acid ethyl ester; 3- (4-fluorobenzylidene) · 1,1-dimethyl -9Heptaphene · 2-ylmethylaminomethylammonyloxy) -1,2,3,6-tetrahydronitrogeno [4,5Hepta] 4 Indole-5-carboxylic acid ethyl ester; C · In a similar manner to step 骡 A, but using 3- (3,4-difluorobenzyl) -8-hydroxy-1,1-dimethyl-1,2,3,6-tetrahydronitrocarbazine And [4,5 hepta] indole-5-carboxylic acid ethyl ester, set 85585 -199 · 200307684 to 3- (4-fluorobenzyl) hydroxy 4,1-dimethyl-1,2,3 , 6-Tetrahydronitropyrene [4,5-b] indole-5-carboxylic acid ethyl ester, and using the appropriate amine, prepared the following compound: 8-cyclopropylamine formamyloxy-3- (3 , 4-Difluorobenzylidene) _1,1_dimethyl_1,2,3,6_tetrahydronitrogeno [4,5_pentole-5-carboxylic acid ethyl ester; MS (ES) 524 (MH +); 3- (4-fluorobenzylidenedimethyl-8-methylamine formamyloxy-l, 2,3,6-tetrahydronitrogen is entrained [4,5 七]wail —5-carboxylic acid ethyl ester; MS (ES): 499 (MH +); and 3 · (3,4-difluorobenzylidene) -ι, ΐ-dimethyl-8- (pyridin-2-ylmethyl) Methylaminomethylammonyloxy) -1,2,3,6-tetrahydronitrocarbazone [4,5_b] indole-5_carboxylic acid ethyl ester; MS (ES): 575 (MH +) · Example 48 3 -(4-Aminobenzyl) _1,1_dimethyl-8- (2_morpholin-4_ylethoxy) -1,2j3,6-tetrahydronitrogen is entrained [4,5 -BH 丨 Preparation of indole-5-acrylic acid ethyl ester

A · 3- (4-fluorobenzylidene) each hydroxy-1,1-dimethyl-1,2,3,6 · tetrahydronitrogen is inferred with [4,5Hepta] indole-5 · carboxyl Ethyl acetate (85 mg, 0.2 mmol), sodium iodide (30 mg), potassium carbonate (140 mg, 1.01 mmol) and 4_ (2_chloroethyl) morpholine (free base, 300 A mixture of milligrams, 2 millimoles) and acetone (8 mL) was heated at 75 ° C for 24 hours. The solid was filtered, and the filtrate was concentrated in vacuo, and the crude product was purified by reverse phase HPLC to give the title compound (11 mg); 1H-NMR (CDC13): δ 10.51 (1 10., s) 5 7.72 ( 1H, s) 5 7.67 (1H5 d), 7.66-7.59 (2H, m), 7.15-7.10 (2H, m), 6.86 (1H, d), 6_76 (1H, dd), 4.27-4 · 17 (4H, m), 4.08 85585 -200- 200307684 (2H, br s), 3.77 (4H, m) 5 2 · 88 (2H, br s), 2.65 (4H, br s), 1 · 59 (6H, s), 1.25 (3H, t); MS (ES): 536 (MH +). B. In a similar manner, but using 1- (2-chloroethyl) hexahydroide, bromine Ethyl acetate or 2-bromoacetamidamine was substituted for 4- (2-chloroethyl) morpholine to prepare the following compounds: 3- (4-fluorobenzyl) -1,1-dimethyl each ( 2-Hexahydropyridin-1-ylethoxy) -1,2,3,6-tetrahydronitrocarba [4,5-b] W indole-5-carboxylic acid ethyl ester; MS (ES): 534 (MH +); 8-ethoxycarbonylmethoxy-3_ (4-fluorobenzylfluorenyl) · ι, ι_dimethyl_i, 2,3,6-tetrahydronitrogen is entrained [4,5 七] 4 丨 Ethyl indole-5-carboxylic acid; MS (ES): 509 (MH +); and 8-aminomethylamidomethoxy-3- (4-fluorobenzylhydrazine) -ΐ, ι_ di Methyl_i, 2,3,6-tetrahydronitrogen Homo [4,5-b] indole-5_carboxylic acid ethyl ester; MS (ES): 480 (MH +) · Example 49 1-Benzyl-3- (4-fluorobenzyl) -1, Ethyl 2,3,6_tetrahydronitrogen

A · 丨 -3-yl-3-phenylacrylonitrile is prepared by the following method: indoxyacetonitrile (2.02 g, 12.9 mmol), MeOH (18 ml), benzoic acid (1.60 ml , 15.5 mmol) and a 25% by weight solution of sodium methoxide in MeOH (3.2 ml '14.2 mmol) were added to a 50 ml flask. The solution was stirred at ambient temperature under N2 for 16 hours. The reaction solution was diluted with DCM (20 ml), molecular sieves (250 g) were added, and the solution was refluxed for 1 hour. The reaction was quenched by the addition of saturated C1 85585 -201- 200307684 (20 ml). The organic phase was separated, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was chromatographed (SiO2, 100% hexane to 5% EtOAc) to give 1.4 g (44% yield) of 2-1H-indole-3-yl-3-phenyl- Acrylonitrile; 1 H NMR (CDC13) 8.42 (1Η, br s), 7.97 (1Η, d), 7.87 (2H, m), 7.63 (1H, s), 7.60 (1H, d), 7.37-7.48 (4H, m), 7 · 25_7 · 33 (2H, m); TLC (Si02 plate, 5: 1 hexane / EtOAc) Rf = 0.35; MS (ESI): 245 (MH +) · B · Benzyltryptamine It was prepared by adding 2-1H-indole-3-yl-3-phenylacrylonitrile (500 mg, 2.04 mmol) and EtOH (25 ml) to 100 ml of N2 scrubbing In the flask. To this solution, approximately 2 grams of Raney-Ni slurry was added. To the reaction solution, hydrazine monohydrate (2.5 ml) was added dropwise and stirred. The reaction solution was stirred at 65 ° C for 4 hours. The slurry was filtered through a celite pad to remove excess Raney-Ni. The filtrate was concentrated under reduced pressure and the crude product was used without further purification; MS (ESI): 251 (MH +). C · 1-benzyl-1,2,3,6_tetrahydronitrogeno [4 , 5-b] Ethyl indole-5-carboxylic acid ethyl ester was prepared in a manner similar to that described in Example 1A, using oligomeric · tryptamine; MS (ESI): 347 (MH +). D · Title Compound System In a manner similar to that described in Example 2A, 1-benzyl-1,2,3,6-tetrahydronitrogen was used to energize [4,5 hepta] indole-5-carboxylic acid ethyl ester with 4-fluoro chloride Made from benzamidine; 4 ^ 111 (00 (313) (5 10.58 (11 ^), 8.07 (11 ^), 7.62-7.66 (211, 11 ^ 7.36 (1H, d), 7.13-7.23 (9H , M), 6.99 (1H, t), 5.25 (1H, dd), 4.26 (2H, m), 3.94 (1H, d), 2.99 (1H, dd), 2.83 (1H, dd), 1 · 22 (3H, t); MS (ESI): 469 (MH +) E. In a manner similar to Step 骡 A, but replacing benzaldehyde with furfural, the following compounds were prepared: 3- (4-fluorobenzylidene) 1-furan-2-ylmethyl-1,2,3,6-tetrahydronitrogeno [4,5 hepta] indole 85585 -202- 200307684 ethyl indole-5-chinoate; MS (ESI) · · 459 (MH +). Example 50 3- (4-Fluorobenzyl) small keto-1,2,3,6-tetrahydronitrogeno [4,5_; 6] pyridine_5-chinic acid Of ethyl ester Preparation billion

A. At 3- (4-fluorobenzylidene) 1,2,3,6_tetrahydronitrogen, [4,5_b] indole-5_carboxylic acid ethyl ester (190 mg, 0.5 mmol) Ear) and DDQ (139 mg, 0.6 mmol), and a mixture of THF-H20 (9: 1, 8 ml) was added at ambient temperature. The reaction mixture was stirred at ambient temperature for 2 hours. Add another 2,3-dichloro-5,6-dicyano-1,4-benzene SQ (DDQ) (139 mg, 0.6 mmol), and stir the mixture at ambient temperature 2 hours. The solvent was removed in vacuo and the residue was dissolved in EtOAc and the bar was washed thoroughly with saturated sodium bicarbonate solution and then with brine. The organic phase was dried over sulfated steel and concentrated in vacuo. The residue was purified by chromatography on stone gum, and was dissolved in hexane-EtOAc (85:15) to give the title compound as a yellow solid (180 mg, 92%); iH-NMR (CDC13): 5 11.4 (lH, s), 8.52-8.48 (2H, m), 7.66-7.62 (2H, m), 7.48-7 · 46 (1H, m), 7.37-7.31 (2H, m), 7.22-7.17 (2H, m), 4.53 (2H, s) 5 4.38 (2H, q), 1.35 (3H, t); MS (ES): 393 (MH +) · B. In a similar manner, but using 10-fluorene oxygen (4-fluorobenzyl) -1,2,3,6-tetrahydronitrogeno [4,5 hepta] indole-5-carboxylic acid ethyl ester, replacing 3- (4-fluorobenzyl) Fluorenyl) -1,2,3,6-tetrahydronitrocarbazone [4,5 VII>? Indole-5-carboxylic acid ethyl ester, the following compounds were prepared: 85585 -203- 200307684 10-fluorenyloxy -3- (4-fluorobenzylidene) -lg isopropyl 1,2,3,6_tetrahydronitrogeno [4,5Hepta] indole-5_carboxylic acid ethyl ester; MS (ES) : 499 (MH +) _ Example S1 1,1-Ethylenedioxy-3- (4 • fluorobenzyl) -1,2,3,6-tetrahydronitrogen [4,5-8] 〃5 丨 Preparation of 5-Ethyl Acetate

3- (4-Fluorobenzyl) small keto · 1,2,3,6-tetrahydronitrogen is entrained with [4,5H &gt; 5 indole-5_carboxylic acid ethyl ester (39 mg, A mixture of 10.1 mmol) and TsOH (10 mg) and ethylene glycol (0.2 ml) in toluene (10 ml) was heated to reflux overnight under nitrogen. After cooling, the reaction was diluted with DCM. Then, it was washed with a saturated aqueous solution of NaHC03 and water, and dried over MgS04. The solvent was evaporated to obtain the crude product, which was purified by column chromatography on silica gel, and was dissolved in MeOH-DCM (2: 98) to give the title compound (7.5 mg); 1H-NMR (CDC13): δ 9 · 68 (1H, s), 8.24 (1Η, d), 7.08 (2Η, m), 7.57 (1Η, s), 7.41 (2Η, m), 7.12 (2Η, m) , 4.77 (2Η, m), 4.55 (2H, m), 4.46 (2H, q), 1.46 (3H, t). MS (ES): 437 (MH +). Example 52 3- (4fluoro Preparation of benzamyl) -l. Meridyl-1,2,3,6_tetrahydroazepine [4,5-BHl indole · preparation of 5-acrylic acid ethyl ester 85585 -204- 200307684

At 3- (4-fluorobenzyl) + keto 4,2,3,6_tetrahydronitrogeno [4,54) fluorene 1 indole-5-metanoate (784 mg, 2 mmol) ) In a suspension of Et0H (ηmL) and AcOH (3mL), NaBH3CN (500mg, 8mmol) was added, and the mixture was stirred at 20 ° C overnight. It was then basified with 28% ammonium hydroxide and extracted with DCM. The combined organic layers were washed with water and dried over MgS04. The solvent was evaporated to obtain the crude product, which was purified by column chromatography on silica gel and dissolved in MeOH-DCM (1: 19) to give the title compound (450 mg); 1H-NMR (CDC13): (5 9.61 (1H, s), 8.41 (1H, m), 7.41 (1H, m), 7.25-7.36 (5Η, m), 7.05 (2Η, m), 4.93 (1Η, m) , 4.57 (1Η, d), 4.42 (3Η, m), 3.85 (1Η, m), 1.35 (3H, d) _ MS (ES): 395 (MH +) · Example 53 1-B Of sulfanyl-3- (4-fluorobenzylfluorenyl) 1,2,3,6_tetrahydronitrogeno [4,5-B] indole-5_resonate ethyl ester

A. In 3- (4-fluorobenzylidene) _1-pyridyl-1,2,3,6-tetrahydronitrogeno [4,5-b] Windole-5-carboxylic acid ethyl ester (60 mg , 0.3 mmol) in DCM (2 ml), at 0 ° C, add trifluoromethanesulfonic anhydride (50 ml, 0.6 mmol), and 85585 -205. 200307684 will / Kun mixture at 0 C: stir for 1 hour. Ethyl mercaptan (34 ml, 0.9 mmol) was added, and the reaction mixture was stirred at 20 ° C overnight. Water was added and the organic layer was separated. The aqueous layer was extracted with DCM. Then, the combined organic layers were washed with water and dried over MgS04. The solvent was evaporated to obtain the crude product, which was purified by column chromatography on Shixi gum and dissolved in MeOH-DCMG: 19) to give the title compound (2 mg); 1H NMR (CDC13): 5 8.59 (1H, s), 8.77 (1H, d), 7.54 (2H, m), 7.36 (1H), 7.19 (1H, m), 7.06 (2H, m) 5 6.73 (1H, s) , 4.41 (2H, m), 4.21-4.30 (3H, m), 2.59-2.69 (2H, m), 1.28 (3H, t), 1.19 (3H, t) · MS ( ES): 439 (ΜΗ +). B · In a similar manner, but replacing the thiol with n-propylamine, the following compounds were prepared: 3- (4-fluorobenzyl) -1_propylamino_i, 2,3,6-tetrahydronitropyrene [4,5-bH 丨 indole-5-carboxylic acid ethyl ester; MS (ES): 436 (MH +). Example 54 3-Methyl-1, 2, 3, Preparation of 6-tetrahydronitrogeno [4,5_BH 丨 indol-5_carboxylic acid ethyl ester

In a solution of 1,2,3,6-tetrahydronitrogenated ethyl [4,5 hept] ardol-5-carboxylic acid (0.15 g 0.6 mmol) in DMF (2 ml), At ° C, add sodium hydride (60%, 28 mg, 0.7 mmol) and MeI solution (38 µl, 0.7 mmol). The mixture was stirred at 0 ° C for 30 minutes. Water was added to the reaction mixture, and 85585 -206- 200307684 was then extracted by DCM. The combined organic layers were washed with water and dried over magnesium sulfate. The solvent was evaporated to obtain the crude product, which was purified by column chromatography on crushed gel, and then dissolved in MeOH_DCM (5: 95), followed by preparative HPLC ^ -step purification 'to give the title compound (86 mg); 1 H_NMR (CDC13): 5 105 (1H, s), 8-26 (1H, m), 7.77 (1H, s), 7.40 (1H, d), 7.31 (1H, d), 7.05 (2H, m), 5.35 (lH, S), 4.28 (2H5q), 3.54 (2H, t), 3.26 (3H, S), 3.14 (2H, m), 1.36 (3H, t) MS (ES): 271 (MH +). Example 55 Preparation of 3-benzyl_1,2,3,6-tetrahydroazepine [4,5-B] oxazol-5 · chitoate

Η Α · Sodium hydride (60% in mineral oil, 320 mg, 8 mmol) was added to ι, 2,3,6-tetrahydronitrogen at 0 ° C and nitrogen [4, 5-b] Indole-5-carboxylic acid ethyl ester (520 mg, 2 mmol) in a stirred solution of anhydrous DMF (8 mL) 'and the resulting mixture was stirred at ambient temperature for 30 minutes. Bromide (345 mg, 2 mmol) was then added dropwise to the above mixture at 0 ° C. The resulting mixture was stirred at ambient temperature for 6 hours. At 〇. 〇, the reaction was quenched by careful addition of ammonium chloride solution. The mixture was extracted with DCM. The combined extracts were washed with saturated ammonium chloride solution, water and brine, dried over sodium sulfate, and evaporated in vacuo to give a brown oil, which was purified by chromatography on silica gel with EtOAc-hexane ( 5: 95) to give the title compound (421 mg); 1h-NMR (CDC13): δ 10.53 (1H? S) 3 7.96 (1H5 s) 5 7.41-7_25 (7H, m), 7.08-6.99 (2H , M), 4.57 (2H, s), 4.33-4.27 (2H, q) 5 3.48 (2H, m), 85585 -207- 200307684 3.01 (2H, m), 1.36 (3H, t); MS (ES): 347 (MH +). B. In a manner similar to that described in step A above, but replacing benzyl bromide with a suitably substituted alkylene or dentyl ether, the following compound was prepared: 3- (2- (Methoxyethyl) -1,2,3,6-tetrahydronitrocarbazone [4,5-b] indolin-5-carboxylic acid ethyl ester; MS (ES): 315 (MH +); and 3, 6-Bis_ (2_methoxyethyl) -1,2,3,6_tetrahydronitrogen indole [4,5seven] indole-5-carboxylic acid ethyl ester; MS (ES): 373 (MH + ); H3-fluoropropyl) -1,2,3,6 · tetrahydronitropyrene [4,5_b] indole-5 ethyl acetate; MS (ES): 317 (MH +); 3-ring Hexylmethyl-1,2,3,6-tetrahydronitrogen denote [4,5-b] 4 丨 Homo-5-carboxylic acid ethyl ester; MS (ES): 353 (MH +); with 3,6-bis-cyclohexylmethyl-1,2,3,6-tetrahydronitrogen inducing [4,5_b] oxindole-5_carboxylic acid ethyl ester; MS (ES): 449 (MH +); 3-ubito-2-ylmethyl-1,2,3,6-tetrahydronitrogen, and [4,5-b; H Ethyl esters; MS (ES): 348 (MH +); 3- (2-morpholin-4-ylethyl) -1,2,3,6_tetracarbazine entrains [4,5VII] indole · 5-Ethyl-chitoate; MS (ES): 370 (MH +); 3-p Titan-3-ylmethyl-1,2,3,6-tetrahydronitrogen [4,5-b] 4 丨 Acetyl-5-methylacetate · MS (ES): 348 (MH +). Example 56 3- (4-fluorobenzylidene) aspartyl-3-1,2,3,6-tetrahydro Preparation of [4,5_: 6] nitrogenated methydoline-5_carboxy warm ethyl ester

85585 -208- 200307684 At _78 ° C, LDA (1.2 mmol) was added to 3- (4-fluorobenzyl) -1,2,3,6-tetrahydronitrogen [4 , 5VII] Indole carboxylic acid ethyl ester (the compound of Example 2A: 378 mg '1 mmol) in THF, and the reaction mixture was slowly warmed to 0 ° C, and at 0 ° C Stir for 30 minutes. Mel (125 ml, 2 mmol) was added and stirred at 20 ° C for 1 hour. The reaction mixture was quenched with water. The organic layer was separated and the aqueous layer was taken in DCM. The combined organic layers were washed with water and dried over MgS04. The solvent was evaporated to obtain the crude product, which was purified by chromatography on silica gel, and was isolated with EtOAc-hexane (1: 4) to give the title compound (27 mg). 1H-NMR (CDC13) ... 5 (1H, s), 7.54-7.60 (3H, m), 7.32 (1H, d), 7.25 (1H, m), 7.14-7.17 (3H, m) 5 4 · 14-4 · 28 (4H, m), 3.61 (3H, s), 3.17 (2H, m), 1.25 (3H, t); MS (ES) ·· 392 (M +), 415 ( MNa +). Example 57 3- (3,4-difluorobenzylidene) -i, i, 6_trimethyl_i, 2,3,6_tetrahydronitrogen is entrained [4,5 »b] Indole-5 · etanoic acid and 1,1,3,6-tetramethyl_i, 2,3,6-tetrahydronitrogen appeal [4,5 ^] 4 丨 larynx_5_traitoric acid Preparation of esters

In 3- (3,4-difluorobenzylidene) _ι, ι · dimethylxin, 2,3,6-tetrahydronitrogeno [4,5Hepta] indole-5-carboxylic acid ethyl ester (21 mg, 0.05 mmol) in a solution of DMF (2 ml) at 0 ° C, NaH (60%, 4 mg, 2 eq) was added, and the reaction mixture was at 0 ° C Stir for 30 minutes. Methyl iodide was added, and the reaction mixture was stirred at 0 ° C for 15 minutes, and then the reaction was quenched with water / AcOH. The mixed 85585-209-200307684 was diluted with DCM, washed with water, and dried over MgS04. The solvent was evaporated to obtain a crude product, which was purified by chromatography on silica gel and dissolved in MeOH-DCM (1:19) to obtain 57 &amp; (2 mg) and 571 &gt; (5 mg); 57 &amp;: 11 ^ 11 ( € 〇0: 13) · Occupies 7.85 (1H, d), 7.46 (2H, m), 7.33 (2H, m), 7.24 (2, m), 7.12 (1H, m), 4.20 (2H, q), 4.00 (2H, s) 5 3.56 (3H, s), 1.63 (6H, s), 1.39 (3H, t) · MS (ES): 439 (MH +); 57b: ^ MRCCDCls) : 5 7.81 (1H)? 7.71 (1H) 7.24 (15 m)? 7.11 (1H? M), 7.00 (1H, m), 4.24 (2H, q), 3.40 (3H, s), 3.19 (3H , S), 1.62 (6H, s), 1.27 (3H, t). MS (ES): 313 (MH +). Example 58 1,2,3,4,5,6_hexahydro_nitrogen hydride [4,5-: 6] Preparation of ethyl indole-5-carboxylic acid

A. The title compound was prepared in a manner similar to that described in Kuehne et al. (J. Org. CAem. 1985, 50, 919-924) and European Patent EP 064317 B1; MS (ES): 259 (ΜΗ +). φ Β · In a manner similar to Example 2A, but using 1,2,3,4,5,6-hexahydronitrogen to inhale [4,5-b] M 丨 Homo-5_resonate ethyl ester, replacing 1, [4,5-b] p5 | Hydroxy-5-carboxylic acid ethyl ester was synthesized by 2,3,6-tetrahydronitrogen, and 4-fluorobenzidine chloride was replaced with benzamidine chloride to prepare the following compounds: 3- (4-fluorobenzylidene) -1,2,3,4,5,6-hexahydronitrobenzyl [4,5hepta] indole-5-carboxylic acid ethyl ester; 1H-NMR (CDC13 ): 5 8.43 (1H, m), 7.31-7.52 (4H, m), 6.96-7.19 (4H, m), 3.96-4.33 (6H, m), 3.67 (2H, m), 3.14 ( 1H, m), 2.94 (1H, m) 5 1.15-1.36 (3H, m); MS (ES): 381 (MH +). 85585 -210- 200307684 C. In a manner similar to step B, but using an appropriate replacement Sulfonium chloride, isocyanate or chloroformate, replacing the benzophenazine chloride, to prepare the following compounds: 3-Benzylfluorenyl-1,2,3,4,5,6-hexahydro-nitrogen [4,5Hepta] Ethyl-5-carboxylate; MS (ES): 363 (MH +); 3- (4-Third-butyl-benzylidene) -1,2 , 3,4,5,6-Hexahydro-nitrogeno [4,5Hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 363 (MH +); 3-phenylethyldonyl-1, 2,3,4,5,6-Hexaazine_nitrogen [4,5-1)] ^ 75 丨 Acetyl-5-methylacetate; MS (ES): 377 (MH +); 3- (3 -Phenyl-propionyl) -1,2,3,4,5,6-hexahydro-nitrogeno [4,5-b] oxindole-5-carboxylic acid ethyl ester; MS (ES): 391 (MH +); 3- (4-Chlorobenzyl) -1,2,3,4,5,6-hexahydro-nitrogen [4,5-1)] zolin-5-carboxylic acid Ethyl ester; MS (ES): 391 (MH +); 3- (2,4-dichlorobenzyl) -1,2,3,4,5,6-hexahydro-nitrogeno [4,5 -Noisy? Ethyl indole-5-carboxylic acid; MS (ES): 431 (MH +); 3- (3-methoxybenzyl) -1,2,3,4,5,6-hexahydro -Nitrogen [4,5 hepta] oxindole-5-carboxylic acid ethyl ester; MS (ES): 393 (MH +); 3- (benzo [1,3] dioxolene-5-carbonyl) -1,2,3,4,5,6-Hexahydronitrogenate [4,5Hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 407 (MH +); 3- (4-nitro Methyl benzamidine) -1,2,3,4,5,6-hexahydro-nitrogeno [4,5 hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 408 (MH +) ; 3- (4-Methoxybenzyl) 1,2,3,4,5,6-hexahydro-nitrogeno [4,5Hepta] eardoline-5-carboxylic acid ethyl ester; MS (ES ) · 393 (MH +); 3- (4-methyl-3-nitrobenzyl Yl) -1,2,3,4,5,6-hexahydro-nitrogeno [4,5 hepta] oledo- 85585 -211-200307684 5-carboxylic acid ethyl ester; MS (ES): 444 (MNa + ); 3- (4-methoxyfluorenyl-benzylidene) -1,2,3,4,5,6-hexahydronitrile [4,54 &gt;] $ 丨 -5-carboxylic acid ethyl Esters; MS (ES): 421 (MH +); 1,4,5,6-tetrahydro-2H-nitrogeno [4,5 hepta] indole_3,5 · dicarboxylic acid 3- (4_chloro Phenyl) 5-ethyl ester; MS (ES) ·· 435 (MNa +); 3- (4-chlorophenylaminemethylmethyl) -1,2,3,4,5,6-hexahydronitrogen And [4,5-1)] indium-5-acrylic acid ethyl ester; MS (ES) · 434 (MNa +); and 3-p.tolylaminomethylamido-1,2,3,4, 5,6-Hexahydro-azepine [4,5H &gt; 5 丨 Ethyl-5-carboxylic acid ethyl ester; MS (ES): 392 (MH +) · D. In a manner similar to that described in step B, However, 3,4-difluorobenzidine chloride and 1,1_dimethyl 4,2,3,4,5,6-hexahydronitrogen, which is produced in a manner similar to that described in Step A [ 4,5-bH 丨 indole-5-carboxylic acid ethyl ester to prepare the following compound: 3- (3 + difluorobenzyl) -1,1-dimethyl-1,2,3,4,5, 6-Hexahydronitrogeno [4,5Hepta] oxindole-5-carboxylic acid ethyl ester; MS (ESI): 427 (ΜΗ +). Example 59 N-methyl 1,2,3,4,5, 6_Hexahydrogeno [4,5-B] Indole-5-urea Equipment

NHMe A. 1,2,3,4,5,6-hexahydronitrogen is entrained with [4,5-b] indole-5-carboxylic acid ethyl ester (1.29 g, 5 hamol; European patent EP 064317 B1) and methylamine hydrochloride (0.67 g, 10 mmol) were added to a solution of methylamine in THF (2 M, 15 ml), and the suspension was heated in a sealed tube under nitrogen under nitrogen. To 80 ° C, stirring for 72 hours. The solvent was evaporated to obtain the crude product, which was purified by chromatography on silica gel with 85585 -212- 200307684

MeOH-DCM (1: 9 to 1: 4) was dissolved to give the title compound (0.8 g); 4-NMR (CDC13): 6 8 · 46 (1H, br s), 8.24 (1H, s ), 7.48 (1H, d),), 7.30 (1H, d), 7.16 (1H, m), 7.10 (1H, m), 3.70 (1H, d), 3.66 (1H, dd), 3_46 (1H, dd), 3.08 (2H, m), 2_87 (2H, m), 2.73 (3H, d), 1.9 (1H, br s); MS ( ES): 244 (MH +) · B_ In a similar manner, but using methylamine and its hydrochloride to replace methylamine and its hydrochloride, the following compounds were prepared: ethyl ethyl 1, 2, 3, 4, 5, 6- Hexahydrogen is entrained with [4,5 hepta] indole_5-service; 11 «^] ^ 11 (0〇 (: 13): δ 8.70 (1H, br s), 8.37 (1H, br s) 5 7 · 48 (1H, d), 7.47 (1H, d), 7.14 (1H, m), 7.08 (1H, m), 3.64-3.68 (2H, m), 3.44 ( 1H, m), 3.20 (2H, m), 3.08 (2H, m), 1.08 (3H51); MS (ES): 258 (MH +). Example 60 N-methyl 3- (4-fluorobenzyl) Fluorenyl) _1,2,3,4,5,6-Hexargon-Nitral [4,5-8] Preparation of Metodo-5aurea

Α · The title compound was used in a manner similar to that described in Example 2A, using N-methyl 1,2,3,4,5,6-hexahydronitrocarba [4,5Hepta] indole-5-urea and Made from 4-fluorobenzyl chloride; iH-NMRCCDCL): δ 9.49 (lH, brs), 7.35 (3H, m), 7.24 (lH, m), 7.14 (4H, m), 4.30 (2H , M), 4.19 (1H, m), 3.69 (2H, m), 3.07 (1H, m), 2.91 (1H, m), 2.78 (3H, brs); MS (ES): 366.2 (MH +) B. In a similar manner 'the above N-methyl 1,2,3,4,5,6-hexahydronitrogen is inducing [4,5 VII] oxindole-5-urea to N-ethyl 1 ， 2,3,4,5,6-hexahydronitrogen benzo [4,5 hepta] indole-5_urea substitution 200307684 to obtain N-ethyl 3- (4-fluorobenzyl) _1, 2,3,4,5,6-Hexahydrogen entrains [4,5 七] 〃5 丨 lar_5-urea. Example 61 Preparation of N-methyl 3- (4-fluorobenzylidene) -1,2,3,6-tetrahydronitrogeno [4,5-8] 4indol-5-urea

A. N-methyl 3- (4-fluorobenzylidene) _1,2,3,4,5,6-hexahydronitrocarba [4,5Hepta] indole-5-urea and TEA To the solution in DCM, a cooled (0 ° C) solution of tertiary-butyl hypochlorite (57 ml, 0.5 mmol) in DCM was added at 0 ° C. The reaction mixture was stirred at 0 ° C for 1.5 hours. Add cold water to wash the solution. The organic layer was separated and the aqueous layer was extracted with DCM. The combined organic layers were washed with water and dried over MgS04. The solvent was evaporated to obtain the crude product, which was purified by chromatography on silica gel and dissolved in MeOH-DCM to give the title compound (14 mg); 1H-NMR (CDC13) · 510.04 (1H, br s), 7.57 ( 2H, m), 7.52 (1H, d), 7.37 (1H, d), 7.24 (1H, m) 5 7 · 12 (4H, m) 5 · 9 (1H, br s), 4.15 (2H, t) , 3.27 (2H, t) 5 2.92 (3H, d); MS (ES): 378 (MH +) · B. In a similar manner, but using N-ethyl1,2,3,4,5,6 -Hexahydronitrogenates [4,5Hepta] pyridin-5 · urea, replacing N-methyl 3- (4-fluorobenzyl) -1,2,3,4,5,6-hexahydro Nitrogen [4,5-b] indole-5-urea produces the following compounds: N-ethyl 3- (Φfluorobenzyl) -1,2,3,6-tetrahydronitrogen [ 4,5 hepta] indole-5-urea; 1H-NMR (CDC13): δ 10.05 (1Η, br s), 7.57 (2Η, m), 7.52 (1Η, d), 7.37 (1Η, d), 7.21 (1H, m), 7.12 (5H, m) 5.88 (1H, br s), 4.15 (2H, t), 3.27 (2H, t), 3.40 (2H, 85585 -214- 200307684 m), 1.19 (3H, t); MS (ES): 378 (MH +). Example 62 3-phenyl-1, 2, 3, 4, 5, 6-hexahydro · nitrogen Preparation of [4,5-BH 丨 Hang_5_carboxylic acid ethyl acetate]

A · Ethyl 1,2,3,4,5,6-hexahydronitrogen is infused with [4,5 hepta] indole 5-carboxylic acid ethyl ester (520 mg '2¾ mol), copper cool acid (728 mg, 4 millimoles), a mixture of phenyldiazonium boron (490 mg, 4 moles) and pyridine (0.35 ml, 4 mmol) in anhydrous DCM (20 ml), and stirred at ambient temperature for 3 days . The mixture was filtered through a celite pad. The filtrate was concentrated in vacuo, and then purified by chromatography on silica gel and dissolved with EtOAc-hexane (7:93) to give the title compound (53 mg); iH-NMR fDCls): (5 8.66 (lH, s ), 7.42 (lH, d), 7.26-7.18 (4H, m), 7.10_7 · 00 (2H, m), 7_69 (2H, m), 6.67 (1H, t), 5.22 (1H , M), 4 · 40_4 · 18 (3H, m), 4.04-4.01 (1H, m), 3.98-3 · 88 (1H, m), 3.58-3.52 (1H, m), 3.22-3.15 ( 1H, m), 3.08-3.02 (1H, m) 5 1.27 (3H51); MS (ES): 335 (MH +). B · In a manner similar to that described in Example 61A, use 3 derived from step 骡 A -Phenyl-1,2,3,4,5,6-hexahydronitrogen benzo [4,5seven] 4 indole-5-carboxylic acid ethyl ester to prepare the following compound: 3-phenyl-1,2 , 3,6-Tetrahydronitrogeno [4,5Hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 333 (MH +). C. In a manner similar to that described in step A, but Using 3-methoxyphenyldihydroxyborane instead of phenyldihydroxyborane, the following compounds were prepared: 85585 -215- 200307684 3- (3-methoxyphenyl) -1, 2, 3, 4, 5, 6 -Hexahydro-azepine [4,5Hepta] indole 5-carboxylic acid ethyl ester; MS (ES): 365 (MH +). Example 63 3- (4_fluorobenzyl Yl) tetrahydro _1,2,3,6- nitrogen and sipping [4,54], Ye voice -5_ group Amides of carboxylic acid prepared / λ

A. 1,2,3,4,5,6-Hexahydrogenohydride [4,5 ethyl hepta-5-carboxylic acid ethyl ester (0.46 g, 1.8 mmol) in DCM (6 ml ), Add 4-fluorobenzidine chloride (0.26 ml, 1.2 equivalents) and TEA (0.38 ml, 1.5 equivalents), and stir the mixture at 2 (rc) 1 hour. The solvent was evaporated to obtain the crude product, which was purified by column chromatography on silica gel and dissolved in MeOH-DCM (1: 9) to give 3- (4-fluorobenzyl) -1,2 , 3,4,5,6-Hexazone nitrogen benzo [4,5Hepta> 5 indole 5-carboxylic acid ethyl ester; (543 mg, 80%) MS (ES): 381 (ΜΗ +). B. In 3- (4 • fluorobenzylidene) -1,2,3,4,5,6-hexahydronitrocarba [4,5-1) ethyl indole-5-carboxylic acid (543 (Mg, 1.42 mmol) in a solution of 1,4-dioxolane (8 ml), and an aqueous solution of sodium hydroxide (114 mg in 2 ml of water) was added. The mixture was stirred at 20 ° C for 1 hour. Then, the solvent was removed under high vacuum to obtain a crude product, which was redissolved in water and acidified with AcOH. The solid was collected by filtration, washed with water, and dried under high vacuum to give 3- (4-fluorobenzylidene) _1,2,3,4,5,6-hexahydro-nitrogeno [4 , 5VII] 4 丨 indole-5_ acid (421 mg, 84%); MS (ES): 353 (MH +). 85585 -216- 200307684 c. In 3_ (4-fluorobenzyl) -1 Suspension of 2,3,4,5,6-hexahydronitrogen [4,5 VII; ^ 丨 -5, carboxylic acid (Π 6 mg, 0.5 mmol) in DCM (3 ml) To the solution, carbonyldiimidazole (97 mg, 0.6 mol) was added, and the mixture was stirred at 2 ° C for 1 hour. Amidine (109 µl, 1 mmol) was added, and the mixture was stirred overnight The solid was collected by filtration, washed with DCM, and dried under high vacuum to give the title compound (90 mg); 93% MS (ES): 442 (MH +) _ D · In a manner similar to that described in Example 61 , But using 3- (4-fluorobenzylidene) -1,2,3,4,5,6-hexahydronitrobenzyl [4,5 hepta] indole-5-carboxylic acid benzylfluorenamine, Substituting N_methyl 3- (4-fluorobenzylidene) -1,2,3,4,5,6-hexahydronitrogen and [4,5 hepta] earminol-5-urea to prepare the following compounds : 3- (4-fluorobenzylidene) -1,2,3,6-tetrahydronitropyre [4,5-b] Indole-5-carboxylic acid benzylphosphonium amine; 1 H-NMR (CDC13): 610_13 (1H, s), 7.45 (3H, m), 7.37 (1H, d), 7.30 (3H, m ), 7.22 (4H, m), 7.12 (4H, m), 6.16 (1H, s), 4.53 (1H, d), 4.15 (2H, t), 3.27 (2H, t); MS (ES): 440 (MH +). E. The following compounds were prepared in a manner similar to that described in steps A to D, in step C, using the appropriate amine, hydrazine, alcohol, phenol or thiol: 3- ( 4-Fluorobenzyl) -1,2,3,6-tetrahydroazepine [4,5Hepta] earmidine-5-carboxylic acid cyclobutylphosphoniumamine; 1H-NMR (CDC13) · 510.00 (1H, s), 7.58 (2H, m), 7.51 (1H, d), 7.36 (1H, d), 7.09-7.24 (5H, m), 6.04 (1H, m), 4.45 (1H, q), 4.14 (2H, t), 3.26 (2H, t), 2.40 (2H, m), 1.86 (2H, m), 1.76 (2H, m); MS (ES ): 404 (MH +); [3- (4-fluorobenzylidene) -l, 2,3,6-tetrahydronitrocarba [4,5-b] indol-5-yl] hexahydropyridine Small group-methanone; MS (ES) · 418 (MH +); [3- (4-fluorobenzylidene) -l, 2,3,6-tetrahydronitropyrene [4,5-b; H 丨 indol-5-yl] morpholine-4-yl-methanone; MS (ES): 420 (MH +); 85585 -217- 200307684 3- (4-fluorobenzyl) -1, 2, 3 , 6_tetrahydronitropyre [4,5-b] ^ indole-5-carboxylic acid (ι_methyl_1H-benzimidazol-2-yl) fluorenamine; MS (ES): 479 (MH +) ; 3- (4-Fluorobenzyl) -l, 2,3,6-tetrahydronitrogeno [4,5 hepta] indole-5-carboxylic acid propylamidine; MS (ES): 392 (MH +); 3- (4 • fluorobenzylidene) -l, 2,3,6-tetrahydronitrocarba [4,5 七] 嘀 -5-carboxylic acid tert-butylamidamine; MS (ES): 406 (MH +); [3- (4 · Fluorobenzyl) -1,2,3,6-tetrahydronitrogen [[5,7]] oldolejyl]-(4 -Methyl-hexahydropyridine-1_yl) -methanone; MS (ES): 433 (MH +); 3- (4-fluorobenzylidene) _1,2,3,6_tetrahydroazepine Benzene [4,5-b] indox-5-carboxylic acid cyclohexylamidoamine; MS (ES): 432 (MH +); 3- (4-fluorobenzoate) -1,2,3,6-tetrakis Hydrogen-nitrogen enantio [4,5-b] p5 丨 Homo-5-chinoic acid, p-Hydro-2-methylamine; MS (ES): 427 (MH +); 3- (4-fluorobenzyl) -1,2,3,6-tetrahydronitrocarba [4,5-b] 4 丨 Homo-5-carboxylic acid (2-dimethylamino-ethyl) amidine; MS (ES): 421 ( MH +); 3- (4-fluorobenzylidene) -l, 2,3,6-tetrafluorenazine is benzo [4,5-b] pyridin-5-chioic acid isopropylamidine; MS ( ES): 392 (MH +); 3- (4-fluorobenzylidene) -l, 2,3,6-tetrahydronitrocarba [4,5-b] indole · 5-carboxylic acid di Hydrazine; MS (ES) ·· 378 (ΜΗ +); 3- (4-fluorobenzyl) -1,2,3,6-tetrahydronitrogen [4,5Hepta] oxindole- Cyclohexylmethylfluorenamine 5-carboxylic acid; MS (ES): 446 (ΜΗ +); 3- (4-fluorobenzyl) -1,2,3,6-tetrahydronitrogen [4, 5 Hepta] indole (pyridylmethyl) pyridine; MS (ES): 441 (MH +); 3- (4-fluorobenzyl) -1,2,3,6-tetrahydronitrogen Allofluorene [4,5 hepta] oxindole-5-chinoic acid allylphosphonium amine; MS (ES): 390 (MH +); 85585 -218- 200307684 3- (4-fluorobenzyl) -1, 2,3,6-tetrahydronitropyrene [4,5 heptamidine-5_carboxylic acid cyclopropylamidamine MS (ES): 390 (MH +); 3- (4-fluorobenzyl)- 1,2,3,6-tetrahydroazepine [4,5 hepta] indole-5_carboxylic acid (2-deca-ethyl) fluorenamine; MS (ES): 396 (MH +); 3- ( 4-fluorobenzylmethyl) -l, 2,3,6-tetramethylazepine, [4,5_b] K 丨 Homo-5-metanoic acid (2-methoxyethyl) pyridine; MS (ES ): 408 (MH +); 3- (4-fluorobenzylidene) -1,2,3,6-tetraazaazepine [4,5Hepta] indole-5_carboxylic acid cyclopropylmethyl Amidine; MS (ES): 404 (MH +); 3- (4ibenzoate) -1,2,3,6-tetrahydronitrogen, and [4,5 七] # 丨 hro_5_ Butylphosphonium amine; MS (ES) · 406 (MH +); 3- (4-fluoro (Methylfluorenyl) -l, 2,3,6-tetrahydronitrocarba [4,5-b] W 丨 Hydroxy-5-carboxylic acid second-butylphosphonium amine; MS (ES): 406 (MH +) ; 3- (4-Fluorobenzyl) -1,2,3,6-tetrahydronitrocarba [4,5 七] 〃5 丨 Threonylphenylphosphonium amine; MS (ES) : 426 (MH +); 3- (4-fluorobenzylidene) _1,2,3,6-tetrahydronitrogen indeno [4,5_b] indole-5-carboxylic acid (2,2,2-tri Fluoroethyl) fluorenamine; MS (ES): 432 (MH +); 3- (4-fluorobenzylidene) _1,2,3,6_tetrahydronitrogen inducing [4,5- 冲 5 丨 in _5_ oxazol-2-ylcarboxylic acid carboxylic acid; MS (ES): 433 (MH +); 3- (4-fluorobenzyl) -1,2,3,6-tetrahydronitrogen [ 4,5-b] Indole-5-carboxylic acid cyclopentylamidoamine; MS (ES) ·· 418 (MH +); 3- (4-fluorobenzylidene) · 1,2,3,6- Tetrahydronitrogero [4,5-bH 丨 indole-5-carboxylic acid cyclobutyl ester; 1H-NMR (CDC13) · δ 10.50 (1H, s), 8.03 (1H, s), 7_63 (2H, m ), 7.52 (1H, d), 7.28 (1H, d), 7.15-7.22 (3H, m), 7.11 (1H, dd), 5.10 (1H, m), 4_21 (2H, t), 3.27 ( 2H, t), 1.96 (2H, m), 1.81 (2H, m), 1.66 (2H, m); MS (ES) · 405 (MH +); 85585 -219- 200307684 3- (4 -Fluorobenzyl) -1,2,3,6-tetrahydronitrogen entrains [4,5-b] -Second-butyric acid; MS (ES): 407 (MH +); 3- (4-fluorobenzyl) · 1,2,3,6-tetrahydronitrogen [4,5 七] 2-Methylamino ethyl benzo-5-carboxylic acid; MS (ES): 422 (ΜΗ +); 3 · (4-fluorobenzyl) -1,2,3,6-tetrahydronitro Homo [4,5-order? 丨 Indole-5-carboxylic acid 1-methyl-allyl ester; MS (ES) ·· 405 (MH +); 3- (4-fluorobenzyl) 4,2 , 3,6-tetrahydronitropyre [4,5-bM 丨 methoxy-5-carboxylic acid 2-methoxyethyl ester; MS (ES) ·· 409 (MH +); φ 3- (4-fluorobenzene Methenyl) -1,2,3,6-tetrahydronitrogen [4,5Hepta], 5 丨 Indole-5-carboxylic acid 2,2-dimethylpropyl ester; MS (ES): 421 ( ΜΗ +); 3- (4-fluorobenzylidene) -1,2,3,6-tetrahydronitrocarba [4,5Hepta] oldole-5-carboxylic acid isobutyl ester; MS (ES) : 407 (MH +); 3- (4-fluorobenzylidene) -l, 2,3,6-tetrahydronitrocarba [4,5Hepta] role-5-carboxylic acid 3-dimethylamino Propyl ester; MS (ES): 436 (ΜΗ +); 3- (4-fluorobenzyl) -1,2,3,6_tetrahydronitrogen [[4,5 七]] radol-5_ Butyl carboxylate; MS (ES): 407 (MH +); _ 3- (4-fluorobenzylidene) -l, 2,3,6-tetrahydronitrogen [4,5Hepta] indole- Cyclopentyl 5-carboxylic acid; MS (ES): 419 (MH +); 3- (4-fluorobenzylidene) -l, 2,3,6-tetra Nitrogen cyclohexyl [4,5 hepta] indole-5-carboxylic acid; MS (ES): 433 (MH +); 3- (4-fluorobenzyl) -1, 2, 3, 6. · Hydrogen and nitrogen allo [4,5 hepta] indole-5-carboxylic allyl ester; MS (ES): 391 (MH +); 3- (4-fluorobenzyl) -1,2,3,6 -Tetrahydronitrogeno [4,5 hepta] indole-5-carboxylic acid 1-ethylsulfonyl propyl ester; MS (ES): 419 (MH +); 85585 -220- 200307684 3- (4-fluorobenzyl) Fluorenyl) 1,2,3,6_tetrahydronitrogeno [4,5_b; N indole 5-phenyl carboxylic acid ester; MS (ES): 427 (MH +); 3- (4-fluorobenzidine Radical) -l, 2,3,6-tetrahydronitrogeno [4,5-b; benzyl N-dole-5-carboxylic acid; MS (ES): 444 (MH +); 3- (4-gasbenzene Methionyl) 1,2,3,6 · tetrazolium hydride [4,5-b] p5 丨 Homo-5-carbonthio fei S_ ethyl ester; 1H-NMR (CDC13): 510.13 (1H, s ), 7.99 (1H, s), 7.64 (2H, m), 7.53 (1H, d), 7.37 (1H, d), 7.10-7.24 (4H, m), 4.23 (2H, t), 3.28 (2H, t), 2.94 (2H, m), 1.63 (3H, t); MS (ES): 395 (MH +); 3- (4-fluorobenzyl) ) -L, 2,3,6-tetrahydronitrogeno [4,5-b] indole-5-carbothioic acid S-propyl ester; MS (ES): 409 (MH +); 3- (4 -Fluorobenzyl))-1,2,3,6-tetrahydronitrogen is [4,5-b &gt;?丨 Indole-5-carbothioic acid S-isopropyl ester; MS (ES): 395 (MH +); 3- (4-fluorobenzylidene) -1,2,3,6-tetrahydronitrogen [4,5-bHI indole-5-carbothioic acid second-butyl ester; MS (ES): 423 (MH +); 3- (4-fluorobenzyl) -1, 2, 3, 6- Tetrahydronitrogenates [4,5Hepta] pyridin-5-carbothioic acid S-second-butyl ester; MS (ES): 423 (MH +);% 3- (4-fluorobenzyl) -1,2,3,6-tetrahydronitrogen benzo [4,5seven] indole-5-carbothioic acid S-isobutyl ester; MS (ES): 423 (MH +); 3- (4- Fluorobenzyl) -1,2,3,6-tetrahydronitrocarba [4,5Hepta] indole-5-carbonthio acid S-third-butyl ester; MS (ES): 423 ( MH +); 3- (4 · fluorobenzylidene) -1,2,3,6-tetrahydronitrogen [4,5-1)] indole-5-carboxylic acid N ', N'-di Methylhydrazine; 1 H-NMR (CDC13): δ 9 · 88 (1H, s), 7.58 (2H, m), 7.51 (1H, d), 7.37 (1H, d), 7.23 (1H, m) , 7.09-7.16 (4H, m), 6.62 (1H, s), 4.14 (2H, t), 3.25 (2H, t), 2.62 (6H, s); MS (ES) : 393 (MH +); 85585 -221- 200307684 3- (4-fluorobenzylidene) -l, 2,3,6-tetrahydronitrocarba [4,5-b] pyridin-5-carboxylic acid (2 and 2-trifluoroethylene) hydrazine; 1H-NMR (CDC13): 5 9 · 65 (1H, s) , 9.39 (1H, s), 8.15 (1H, s), 7.51_7 · 57 (3Η, m), 7.45 (1Η, m), 7.23 (1Η, d), 7.12- 7.19 (4Η, m), 4.16 (2Η, t), 3.27 (2H, t); MS (ES): 445 (MH +). F. In a similar manner as described in steps 骡 A to D, but use 2-methyl-1,2,3,4,5,6-hexahydronitrocarbazone [4,5 hepta] indole-5_carboxylic acid ethyl ester, replacing 1,2,3,4,5,6 -Hexahydronitrogeno [4,5 hepta] indole-5-carboxylic acid ethyl ester; and benzylamine was replaced with cyclobutylamine to prepare the following compounds: 0 3_ (4 · fluorobenzyl) -2- Methyl-1,2,3,6-tetrahydronitrocarba [4,5Hepta] ardol-5_carboxylic acid cyclobutylamidamine; 1H-NMR (CDC13): 5 9.93 (1H, s), 7.58 (2H, m), 7.49 (1H, d), 7.35 (1H, d), 7.09-7.23 (5H, m), 5.92 (1H, d), 5.45 (1H, s), 4.45 (2H, m), 3.34 (1H, dd), 3.12 (1H, dd), 2.40 (2H, m), 1.72-1 · 89 (4H, m), 1.08 (3H, d ); MS (ES): 418 (MH +). G. In a similar manner to step F, but in step 骡 A, replace the 4-fluorobenzyl chloride with 3,4-difluorobenzyl chloride, The following compounds were prepared: 3- (3,4-difluorobenzylidene) -2-methyl-1,2,3,6-tetrahydronitrogen [4, 57 #] pyridol-5_ #cyclobutylphosphonium carboxylic acid; 1 H-NMR (CDC13): 5 9 · 90 (1H, s), 7.47 (2H, m), 7.36 (1Η, d ), 7.25-7.33 (6Η, m), 7.22 (1Η, m), 7.10 (2Η, m), 5.94 (1Η, d), 5.42 (1Η, s), 4.46 (2H , M), 3.34 (1H, dd), 3.12 (1H, dd), 2.42 (2H, m), 1.88 (2H, m), 1.76 (2H, m), 1.09 (3H, d ); MS (ES): 436 (MH +) · H. In a manner similar to that described in steps 骡 A to D, but in step 1-A, 1-methyl-1,2,3,4,5, 6-Hexahydronitrogeno [4,5Hepta] indole-5-carboxylic acid ethyl ester, replacing 1,2,3,4,5,6-Hexahydronitrogeno [4,5-b] Windole -5-carboxylic acid ethyl ester; preparation of chin 1J compound: 3- (3,4-difluorobenzyl) small methyl-1,2,3,6-tetrahydronitrogen [4,5- b] Indole-5- 85585 -222- 200307684 Cyclobutylammonium carboxylate; 1 H-NMR (CDC13): 5 9 · 99 (1H, s), 7.56 (1H, d), 7.49 (1H, m ), 7.31-7.37 (2H, m), 7.19-7.27 (2H, m), 7.11 (1H, m), 7.05 (1H, br s), 5.97 (1H, m), 5.09 ( 1H, br s), 4.45 (2H, m), 3.75 (1H, m), 3.24 (1H, d), 2.40 (2H, m), 1.86 (2H, m), 1.76 (2H, m ), 1.35 (3H , D); MS (ES): 436 (MH +). I. In a manner similar to that described in step 骡 H, but in step 骡 D, isopropyl alcohol was used to replace cyclobutylamine to prepare the following compound: 3- (3 , 4-difluorobenzyl) small methyl-1,2,3,6-tetrahydronitrogeno [4,5 hepta] indole-5-carboxylic acid isopropyl ester; 1H-NMR (CDC13) : 5 10.54 (1H, s), 7.58 (1H, d), 7.52 (1H, m), 7.37-7 · 42 (2H, m), 7.19-7.31 (5H, m), 7.12 (1H, m ), 5.26 (1H, dd), 5.14 (1H, m), 3.85 (2H, m), 3.18 (1H, d), 1.33 (3H, d), 1.23 (3H , D), 1.20 (3H, d); MS (ES): 425 (MH +). Example 64 3- (3,4-difluorobenzyl) -1,1-dimethyl-1, Preparation of 2,3,6_tetrahydronitrogero [4,5-8] meowdo-5-isopropyl carboxylate

A. Using CDI and isopropanol, 3- (3,4-difluorobenzyl) -1, l-dimethyl-1,2,3,4,5,6-hexahydronitrogen [4,5-bH Acetyl-5-acetate was converted to its corresponding isopropyl ester, and then oxidized according to the procedure of Example 63 to obtain the title compound; 1 H-NMR (DMSO- d6): 5 10.83 (1H, s), 7.76 (1H, d), 7.71 (1H, app t), 7.64 (1H, s), 7.52-7.61 (2H, m), 7.40 (1H, m) , 7.08 (1H, app t), 6_98 (1H, app t), 5.05 (1H, sevenfold peak), 1.52 (6H, s), 1_18 (6H, d); MS (ESI): 439 (MH +) 200307684 B · In a similar manner, using CDI and cyclobutylamine, 3- (3,4-difluorobenzyl) -1,1 · dimethyl-1,2,3,4,5, 6-Hexargon-nitrogen is entrained with [4,5 hepta] oxindole-5-carboxylic acid, and converted to its corresponding cyclobutylamidamine, which is then oxidized as described in Example 63 to obtain cyclobutane. 3 · (3,4 · difluorobenzylidene) -1,1 · dimethyltetrahydroazepine [4,5-b; HH indole-5 · carboxamide; MS (ESI): 450 (ΜΗ ^. Example 65 3- (3,4-difluorobenzylidene) -1,1-tetramethylene-143,6-tetrahydronitrogen degenerates [4 多 8] 哚 引 引 素 酸Otome Prepare

Α · θ 丨 acetonitrile (5 g, 32 mmol), Triton Β (40% in MeOH, 0.5 g), thallium bromide (7.8 ml, 2 equivalents) and aqueous NaOH ( 50%, 12.6 ml), and stirred at 20 ° C for 2 hours. Add water. The solid was collected by filtration, washed with water and hexane, and dried under high vacuum to obtain [1 · fluorenyl-1H-W indol-3-yl] acetonitrile (6.97 g). MS (ES) .. 247 (MH +). Beta. To a suspension of sodium hydride (60%, 2.26 g, 56 mmol), 1-benzyl-1H-Windole-3 was added dropwise. A solution of acetonitrile in DMSO · ether (10 ml: 80 ml), and the mixture was stirred at 20 ° C for 5 hours. Add water and hexane. The solid was collected by filtration, and washed with water and hexane to obtain 1- (1.fluorenyl-1H-indol-3-yl) cyclovaleronitrile (5.3 g). MS (ES): 301 (MH ^) · C · CH> (1H-fluorin-3-yl) cyclopentyl] methylamine is used in a manner similar to that described in Example 32, using 1- (1-benzyl Made from -1H-pyridol · 3 · yl) cyclovaleronitrile; MS (ES): 85585 -224- 200307684 305 (MH +). D · Solution in liquid ammonia (60 ml) in anhydrous THF (20 ml) Inside, sodium metal (1.64 g, 71 mmol) was added in portions. A solution of C- [1- (1H-indole-3-yl) cyclopentyl] methylamine (3.58 g, 11.8 mmol) in THF (20 ml) was added dropwise to the above solution, and Reflux at -33 ° C for 1.5 hours. The reaction mixture was quenched with a saturated aqueous ammonium chloride solution. After ammonia was purged with nitrogen, more water was added and extracted with DCM. The combined organic layers were washed with brine and dried over MgS04. Evaporation of the solvent gave C- [1- (1H-indol-3-yl) cyclopentyl] methylamine as a white solid (2.5 g); MS (ES): 215 (MH +). E. 1, 1_ Tetramethylene-1,2,3,6 · tetrahydronitrogeno [4,5Hepta] indole-5_ethyl acetate is used in a manner similar to that described in Example 1A, using C- [1- (1H_indol-3-yl) cyclopentyl] made from methylamine; MS (ES): 311 (MH +). F. The title compound was prepared in a manner similar to that described in Example 2A, using 1,1-tetracycline Methylene_1,2,3,6_tetrahydronitrogeno [4,5-b; made from ethyl indole-5-carboxylic acid; 1H NMR (CDC13) ·· δ 1〇 · 74 ( 1H, s), 7.74 (1H, m), 7.49 (1H, m), 7.40 (1H, d), 7.34 (1H, m), 7.21 (2H, m), 7.08 ( 1H, m), 4.27 (2H, q), 3.50-4.60 (2H, br s), 2.46 (2H, m), 2.05 (4H, m), 1_69 (2H, m), 1.25 (2H , T) · MS (ES): 451 (MH +) · Example 66 Preparation of 2,3,4,9-tetrahydro-ΙΗ- 凌-卡 淋 -1-carboxylic acid ethyl ester Α 2,3,4, Ethyl 9-tetrahydro-l-carboline carboxylic acid ethyl ester was prepared in the following manner. Tryptamine-HC1 (1.33 g, 6.76 mmol), EtOH (12 ml) and ethyl glyoxylate 50% toluene solution (1.66 g, 8.11 mmol) Was added to 50 ml of N2 gas scrubbing of the flask. The reaction solution was refluxed for 16 hours. The reaction solution was concentrated under reduced pressure, and the resulting crude material was chromatographed (Si02, 100% DCM to 4%) 85585 -225- 200307684

MeOH) to provide 1.10 g (68% yield) of 2,3,4,9-tetrahydro-1H-carboline-1-carboxylic acid ethyl ester; 1 H NMR (CDC13) 5 8 · 59 (1H, br s), 7.46 (1H, d), 7.39 (1H, d), 7.23 (1H, t), 7.14 (1H, t), 5.40 (1H, s), 4. · 24 (2H, q), 3.51 (1H, m), 3.07 (1H, m), 2.86 (1H, d), 1.30 (3H, t); 13CNMR (CDC13) 5 166, 137,126, 123, 122, 120, 119, 112, 108, 64, 60, 53, 41, 14; MS (ESI): 245 (MH +). B. In a similar manner, but using a-methyl-tryptamine-HC1, HD-tryptamine Methyl ester_HC1 or indole-3-yl) propylamine, replacing tryptamine-HC1 to prepare the following compounds: φ 3 · methyl-2,3,4,9-tetrahydro_111- / 3carboline small carboxylic acid Ethyl esters; 2,3,4,9-tetrachloro-1H- / 3 mouth carin-1,3-dijun 1-acetamidine 3-methylamidine; and 4-methyl-2,3,4, Ethyl 9-tetrahydro-1 qin / 5carboline-1-carboxylate;] ^ 8 (£ 81): 259 () ^ 11+). Example 67 2_ (4_fluorophenylfluorenyl) -2, Ethyl 3,4,9-tetrahydro-1H-oligocarboline-1

A. The title compound was prepared by the following method: 2,3,4,9_tetrahydro-1H-coldcarboline small carboxylic acid ethyl ester (102 mg, 418 picomolar), DCE (5 ml), chlorine 4-fluorobenzidine (60 μl, 477 μmol), diisopropylethylamine (167 μl, 954 μmol), DMAP (6 mg, 10 mol%) was added to 25 ml In the flask. The solution was stirred at 55 ° C under N2 for 17 hours. The solution was concentrated under reduced pressure and the crude material was chromatographed (SiO2, 100% hexane to 25% EtOAc) to provide 143 mg (63% yield) of the title compound; iHNMR ^ CDCU) 5 8 · 40 ( lH, br s), 85585 -226- 200307684 7.53-7.57 (3H, m), 7.41 (1H, d), 7.10-7.23 (4H, m), 6.19 (1H, s), 4.31 (2H, m), 4.10 (1H, dd), 3.63 (1H, m), 2.87-2.96 (1H, m), 2.78 (1H, dd), 1.36 (3H, t); 13 CNMR (CDC13) 5 171,169, 138, 130, 129, 126, 126, 123, 120, 116, 116, 112, 110, 62, 53, 45, 22, 14; MS (ESI): 367 _ +) · B. In a manner similar to step A, but replacing 4-fluorobenzyl chloride with acetamidine chloride, the following compounds were prepared: 2-ethylamyl-2,3,4,9-tetrahydrocarboline carboxyl Ethyl Ester; MS (ESI): 287 (MH +). C. In a manner similar to step B above, but using 2,3,4,9-tetrahydro · 1Η-coldcarbolin-1,3-dicarboxylate 1-Ethyl 3-Methyl Ester, Substituting 2,3,4,9-Tetrahydro-1H-Carboline Small Carboxylic Acid Ethyl Ester to Prepare the Following Compound: 2-Ethyl-2,3,4,9 -Tetrahydro-1Η- yScarboline-1,3-dicarboxylic acid 1, ethyl ester 3 methyl ester; MS (ESI): 345 (MH +). D. In a similar step · Step A Method, but using the compound in Example 66B and replacing 2,3,4,9 · tetrahydro_1Η- / 5carboline-1-carboxylic acid ethyl ester to prepare the following compound: 2- (4-fluorobenzidine Ethyl) -3-methyl-2,3,4,9-tetrahydro_ih- / 5-carboline-1-carboxylic acid ethyl ester; MS (ESI): 381 (MH +) (diastereomer The mixture was separated by preparative HPLC with a 5 micron q 8 reverse phase, 120 Angstrom column; the solvent gradient was 30_99% MeCN, within 12 minutes); 2- (4-fluorobenzyl) -2,3 , 4,9-tetrahydro-1H-point · carboline-i, 3-dicarboxylic acid 1-ethyl ester 3-methyl ester; MS (ESI): 425 (MH +); and 2- (4-fluorobenzyl) Fluorenyl) glacial methyl_2,3,4,9_tetrahydro-iHj · carboline small carboxylic acid ethyl ester; MS (ES): 381 (MH +). E · in the manner as described in step A, However, 3,4-difluorobenzyl chloride 85585 -227- 200307684 fluorenyl group was used to replace 4-fluorobenzyl chloride to prepare the following compounds: 2- (3,4-monofluorobenzyl) _2,3 , 4,9_tetrahydro-lH_y5_carboline small carboxylic acid ethyl ester · MS (ESI): 385 (MH +). 'F · In the manner as described in step 骡 E, but using the present methyl valley-carb 1-Ethyl methanoate (the compound in Example 66B), replacing 2,3,4,9_tetrahydrooligocarboline-1 · carboxylic acid Group to prepare the following compounds: 2- (3,4_difluorobenzyl) winter methyl_2,3,4,9-tetrahydrocarboline small carboxylic acid ethyl ester; MS (ESI): 399 (MH + ). Example 68 · 2-(4-fluorobenzyl) -4,4_dimethyl_2,3,4,9_tetrahydro-1H_stone-leaf-1_ preparation

F

A · dimethyl_2,3,4,9-tetrahydro_111- / 3-carboline small carboxylic acid ethyl ester was prepared in a manner similar to that described in Example 66A, with 2 &lt; m • lardole_ 3-ylpyridinemethylpropylamine replaces tryptophan_HC1, which is used during the alkylation of (1_third_butoxyquinol-3-yl) acetonitrile as described in Example 32B Synthesized from 2 equivalents of methyl iodide; MS (ESI): 273 (MH +). B. The title compound was prepared in a manner similar to that described in Example 67A, using 4,4-dimethyl-2,3,4,9- Made from tetrahydro-1 fluorene-stone-carboline carboxylic acid ethyl ester; MS (ES) ·· 395 85585 -228- 200307684 (MH +) · C · In the manner described in step B, but using acetamidine chloride or 3,4_ difluorobenzyl chloride replaced 4-fluorobenzyl chloride to prepare the following compounds: 2-ethylfluorenyl-4,4-dimethyl-2,3,4,9_tetrahydro-1H -/ 5-carboline- 丨 _Ethyl Acetate; MS (ESI): 315 (MH +); 2- (3,4-difluorobenzylcarboxylate) -4,4-dimethyl-2,3, 4,9-tetrahydro-111_ / 5yinlin + ethyl carboxylate; MS (ESI): 413 (MH +) · Example 69 (3,4-«-Gaphenyl)-(1-phenyl-1, Preparation of 3,4,9-tetraazepine leaf leaching-2-yl) -formamidine

Α 1-phenyl-2,3,4,9-tetrahydro-111-non-leaf system was prepared in the following manner, using tryptamine-HC1 (500 mg, 2.54 mmol), CHC13 (20 ml ), Anhydrous Et0H (16 ml), benzaldehyde (520 µl, 5.08 mmol) and TFA (1.9 ml, 25.4 mmol) were added to a 50 ml flask purged with N2. The reaction solution was stirred at ambient temperature for 18 hours and then at 60 ° C for 4 hours. The solution was concentrated under reduced dust: and the crude material was chromatographed (SiO2, 100% hexane to 25% EtOAc) to produce 95 mg of 1-phenyl-2,3,4,9-tetrahydro -1H- / 3-carboline; MS (ESI): 249 (MH +). Β · The title compound was prepared in the following manner, and 1-phenyl-2,3,4,9-tetrahydro-1Η- / 3-folioline (95 mg, 383 micromoles), DCE (5 ml), 3,4-di 85585 -229- 200307684 flubenzimid (88 mg, 498 micromoles), and TEA (1.0 ml ) Add to a 25 ml beaker. The solution was stirred at 55 ° C for 16 hours. The reaction solution was concentrated and the crude sample was chromatographed (SiO 2, 100% hexane to 25% EtOAc) to give 53 mg of the title compound; 1H NMR (CDC13) 5 8 · 02 (1H, br s) , 7.53 (1H, d), 7.30-7.33 (6H, m), 7.15-7 · 23 (5H, m), 7.07 (1H, bi * s), 3.75 (1H, m), 3.41 (1H, m), 2.93 (1H, m), 2.84 (1H, dd); MS (ESI): 389 (MH +). Example 70 (3,4-difluorophenyl)-(l_form Of phenyl-1, phenyl, 1,3,4,9-tetrakis-teolin-2-yl) -methanone

A · methyl small phenyl-1,3,4,9_tetrahydrome-carlin system was prepared by the following method, tryptamine-HC1 (500 mg, 2.54 mmol), 丨 · butanol (12 Ml) and acetophenone (1.5 ml, 13¾ mol) were added to a 25 ml flask connected to a Dean-Stark gas cylinder. During 4 hours of intense reflux, a co-removal of the butanol /% o mixture was performed. The concentrated solution was stirred for another 14 hours at near reflux. The solution was concentrated under reduced pressure. The residue was dissolved in EtOAc (70 mL), washed with saturated NaHCO3 (40 mL x 3), washed with h20 (40 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was chromatographed (si02, 100% DCM to 5% MeOH) to provide 376 mg of μmethyl small phenyl group, which was depleted by hydrogen. 85585 -230- 200307684 Carboline; 1H NMR (CDC13) 6 7 74 (1H, br s), 7.54 (1H, d), 7.23-7.32 (6H, m), 7.09_7 · 21 (2H, m), 3.13 (1H, m), 2.71-2.94 (3H , M), 1.84 (3H, s); 13 CNMR (CDC13) δ 146, 138? 136, 128, 1275 127, 1265 122, 1195 118, 1105 110, 57, 40, 28, 23; TLC (Si02, 10 : 1 DCM / MeOH) Rf = 0.3; MS (ESI): 263 (MH +) · B. The title compound was prepared as follows. 1-methyl-1 · phenyl-1,3,4,9- Tetrahydrocarboline (105 mg, 400 micromoles), CHC13 (9 ml), 3,4-difluorobenzidine chloride (85 mg, 480 micromoles), and DIEA (140 microliters, 800 micromoles) Ear) into a 25 ml flask. The solution was stirred at 60 ° C under N2 for 17 hours. The reaction solution was concentrated and the crude sample was chromatographed (SiO2, 100% hexane to 20% EtOAc) to yield 35 mg of the title compound; 1HNMR (CDC13) 57.54 (1H, d), 7.48 (2H, d) , 7.12-7 · 32 (9H, m), 4.05 (1H, m), 3.64-3.70 (1H, m), 3.19 (1H, m), 2.96 (1H, m), 2.29 (3H, s); MS (ESI): 403 (MH +). Example 71 3- (4-ethoxybenzyl) -l, 2,3,6-tetrahydronitrogen fused 4,5 -8】 Preparation of ethyl indole-5-carboxylic acid ethyl ester

A. In 1,1,2,3,6-tetrahydronitrogen is used to aspirate [4,5-b] indole-5_carboxylic acid ethyl ester (250 μl, 0.2M solution (~ 13 mg), 0.05 mmol ) In a solution in THF, using a robotic pipette, add 4-ethoxybenzidine chloride (500 μl, 02 Lao 200307684 solution (~ 18 mg), 0.1 mmol) and TEA (28 microliters, o. 2 millimoles). The mixture was allowed to stand at 55 C overnight using a circulating oil bath. Add tromethamine resin (~ 30 mg) 'and shake this suspension at 20 ° C for 0.5 hours. After the reaction was blocked, the resin was removed by filtration. The solvent was evaporated to obtain a crude product, which was purified by HPLC-MS to obtain the compound (~ 0.5 mg, based on the ELSD calibration curve, estimated weight); MS (ES): 405 (MH +). B · The following compounds Made in this way using a suitably substituted chlorinated tortoise: 3- (4-fluorobenzylidene) -1,2,3,6-tetrahydroazepine and [4,5 七] indox- Ethyl 5-quinoate; MS (ES): 379 (MH +); 3- (4-Eryl aspartate) _1,2,3,6-tetrakis-nitrogen P and [4,5-b] p5丨 Homo-5_carboxylic acid ethyl ester; MS (ES): 395 (MH +); 3- (4-ethoxybenzyl) -l, 2,3,6-tetrahydronitrogen [4, 5Seven] oxindole-5-carboxylic acid ethyl ester; MS (ES) ·· 405 (MH +); 3- (4-ethylbenzyl) -1,2,3,6-tetrahydronitrogen [4,5-b] Indole-5-carboxylic acid ethyl ester; MS (ES): 389 (MH +); 3- (4-propylbenzylidene) -1,2,3,6-tetrahydro Nitrogen [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES): 403 (MH +); 3- (2-phenoxyethylfluorenyl) -1,2,3,6 -Tetrahydronitrogero [4,5-b] K 丨 Homo-5_carboxylic acid ethyl ester; MS (ES): 391 (MH +); 3- [2- (4-methoxyphenyl) -ethyl alcohol Radical] _1,2,3,6-tetrahydronitrogen benzo [4,5 hepta] indam-5-acrylic acid ethyl ester; MS (ES): 405 (M H +); 3- (2-methoxyethenyl) -l, 2,3,6-tetrahydronitrogen [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES) : 329 (MH +); 85585 -232- 200307684 3- (3-phenylpropanyl) -l, 2,3,6-tetrahydronitrogen [[4,5-1)] Ethyl Ester; MS (ES): 389 (MH +); Methoxypropylammonium) -1,2,3,6-tetrahydronitrogen entrains [4,5 七] Esters; MS (ES): 371 (MH +); 3- (4 · Chlorobutyryl) -1,2,3,6-tetrahydronitrogen-H [[4,5Hepta]] indole-5_ethyl acetate ; MS (ES): 361 (MH +); 3-nononyl-1,2,3,6-tetrahydronitrocarba [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES ) ·· 397 (MH +); 3- (2-Chloro-2-phenyl · ethenyl) -l, 2,3,6-tetrahydronitrogen [4,5_b] W 丨 -5- Ethyl methanoate; MS (ES) ·· 409 (MH +); 3- (3,4,5_trimethoxybenzylidene) _1,2,3,6-tetrahydronitrogen [4,5 Seven] 〃5 丨 Ethyl_5_carboxylic acid ethyl ester; MS (ES): 451 (MH +); 3-cyclopropanecarbonyl-1,2,3,6-tetrahydronitrogen [4,5-b] Indole-5-acrylic acid ethyl ester; MS (ES): 325 (MH +); 3_cyclopentylcarboxyl1,2,3,6-tetrahydroazepine [4,5_b] indole_5 · carboxyl Ethyl Ester; MS (ES) ·· 353 (MH +); 3-cyclohexylcarbonyl-1,2,3,6-tetrahydro Nitrogen [4,5Hepta] indole-5-acetic acid ethyl ester; MS (ES) • 367 (MH +); 3- (3-cyclopentylpropanyl) -l, 2,3,6- Tetrahydronitrogeno [4,5-b] indole-5 · carboxylic acid ethyl ester; MS (ES): 381 (ΜΗ +); 3- (crean_2_carbonyl) -1, 2, 3, 6_tetrahydronitropyrene, μ, 5,7] indole-5 carboxylic acid ethyl ester; MS (ES): 351 _ +); 3- (2-nitrobenzyl) -1, 2, 3, 6-Tetrahydronitrogeno [4,5Hepta-5-carboxylic acid ethyl ester; MS (ES): 406 (MH +); 85585 -233-200307684 3- [2- (3-methoxy-benzene ) -Ethenyl] -1,2,3,6-tetrahydronitrogen [[4,5 七]] lam-5-ethyl carboxylate; MS (ES): 405 (ΜΗ +); 3- (2-Ethyloxy-ethanoyl) -1,2,3,6-tetrahydronitrocarba [4,5-b] 4 丨 Homo-5-acrylic acid ethyl ester; MS (ES): 405 ( MH +); 3- (3-nitrobenzylidene) -l, 2,3,6-tetrahydronitrogeno [4,5-b] 4 | Homo-5-acrylic acid ethyl ester; MS (ES ): 406 (MH +); 3- (Benzo [1,3] dioxo-5-lanyl) -l, 2,3,6-tetraazanitrogen is benzo [4,5-b] p5丨 Vinyl 5-carboxylic acid ethyl ester; MS (ES): 405 (MH +); 3- (2 • phenylbutyridinyl) -1,2,3,6-tetrahydronitrogen [4,5_b; H 丨Indole-5_carboxylic acid ethyl ester; MS (ES): 403 (MH +); 3- (2-methylbutylfluorenyl) -1,2,3,6-tetra Nitrogen [4,5_bHI indole-5 · carboxylic acid ethyl ester; MS (ES): 341 (MH +); 3- (2-chloropyridine_3_carbonyl) -1,2,3,6-tetrahydronitrogen [Ethyl [4,5-b] pyrene-5-carboxylic acid ethyl ester; MS (ES): 396 (MH +); 3- (2,4,6-trifluorobenzyl))-1,2, 3,6-Tetrahydronitrogeno [4,5Hepta] indole-5_carboxylic acid ethyl ester; MS (ES) · 415 (MH +); 3- (2-chlorobutylfluorenyl) -1,2, 3,6-tetrahydronitropyrene [4,5-bHj indole-5-carboxylic acid ethyl ester; MS (ES): 361 (MH +); 3- (benzo [b] pyrimene_2_carbonyl)- l, 2,3,6-tetrahydronitrogeno [4,5seven] 4 indole-5-carboxylic acid ethyl ester; MS (ES) · 417 (MH +); 3- (2-phenylthio- Acetyl) · 1,2,3,6-tetrahydronitrogen is eh [4,5 hepta] oxindole-5-carboxylic acid ethyl ester; MS (ES): 407 (MH +); -Carbonyl) -l, 2,3,6-tetrahydronitrogeno [4,5hepta] oxindole-5-carboxylic acid ethyl ester; MS (ES): 367 (MH +); 85585 -234- 200307684 3- Propionyl-1,2,3,6-tetrahydronitrocarbazone [4,5-b] Ethyl-5-carboxylate; MS (ES): 313 (MH +); 3- (3,5 -Bis · trifluoromethylbenzenesulfonyl) -1,2,3,6-tetrahydronitrogeno [4,5_b] indole-5-carboxylic acid ethyl ester; MS (ES): 533 (MH +); 3- (Toluenesulfonyl) -1,2,3,6-tetrahydronitrogen [4,5Hepta] pyridin-5- Ethyl Ester; MS (ES): 411 (MH +); 3 · benzenesulfonyl-1,2,3,6-tetrahydronitrogeno [4,5-b; Hl indole-5_carboxylic acid ethyl ester ; MS (ES): 397 (ΜΗ +); φ 3 · (telephen-2-sulfofluorenyl) -1,2,3,6-tetrahydronitrogen [4,5Hepta] pyridine_5_ Ethyl carboxylate; MS (ES): 403 (MH +); 3 · (fluoren-2-sulfonyl) -l, 2,3,6-tetrahydronitrogen [4,5-b; H Ethyl-5-carboxylate; MS (ES): 447 (MH +); 3- (3-chloro-4-imidylphenylfluorenyl) -1,2,3,6-tetrahydronitrogen [ 4,5-b] p? 丨 no-5-carboxylic acid ethyl ester; MS (ES): 449 (MH +); 3- (2-chlorobenzene continuation group) -1,2,3,6-tetrahydro Nitrogen [4,5-b] 〃5 丨 Homo-5-acetic acid ethyl ester; MS (ES): 431 (MH +); 3- (4-trifluorofluorenylbenzenesulfonyl) -1, 2,3,6-tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES) ·· 465 (MH +); 3_ (4_isopropylbenzenesulfonyl) ) 1,2,3,6_tetrahydronitrogen benzo [4,5 hepta] indole-5 · carboxylic acid ethyl ester; MS (ES): 439 (ΜΗ +); 3- (3-methylbenzyl) Fluorenyl) -1,2,3,6 · tetrahydronitropyrene [4,5_b; ethyl indole-5-carboxylic acid; MS (ES): 375 (MH +); 3- (3-chloro Benzamidine) -l, 2,3,6-tetraazanitrogeno [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES ): 395 (MH +); 85585 -235- 200307684 3- (2,4-dichlorobenzyl) -l, 2,3,6-tetrahydroazepine [4,5-b] indole- Ethyl 5-carboxylic acid; MS (ES): 429 (MH +); 3- (2-chlorobenzylhydrazyl) -1,2,3,6-tetrahydronitrogen is [4,5_b] indole Ethyl-5-carboxylate; MS (ES): 395 (MH +); 3-Benzylhydratino-1,2,3,6-tetrahydronitrocarba [4,5Hepta] pyridin-5_carboxy Ethyl Ester; MS (ES): 361 (MH +); 3- (3,4-difluorobenzyl) -l, 2,3,6-tetrahydronitrogen [4,5Hepta] indole -5-Ethyl carboxylic acid; MS (ES): 397 (MH +); 3 · (2,5-difluorobenzyl) -l, 2,3,6-tetrahydronitrogen [4,5 VII] Ethyl indole-5-carboxylic acid; MS (ES) · 397 (MH +); 3- (4-cyanobenzyl) -1,2,3,6-tetrahydronitrogen [ 4,5-b: HI indole-5-carboxylic acid ethyl ester; MS (ES): 386 (MH +); 3. · phenethylfluorenyl-1,2,3,6-tetrahydronitrogen [4,5 -b] ethyl indole-5-carboxylic acid; MS (ES): 375 (MH +); 3- (4-methylbenzylidene) -l, 2,3,6-tetrahydronitrogen [ 4,5-b] indole-5-metanoic acid ethyl ester; MS (ES): 375 (MH +); 3- (4-methoxybenzyl) -1,2,3,6-tetrahydronitrogen Epoxy [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES): 391 (MH +); 3- (2,5 · bis-trifluoromethylbenzyl (Methenyl) -1,2,3,6-tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES): 497 (MH +); 3- [3- ( 2-Chloro-6-fluorophenyl) _5_methyl_isosignaron-4-lanyl] -1,2,3,6-tetrahydronitrogeno [4,5 七] adoldol_5_ Ethyl carboxylate; MS (ES): 494 (MH +); 3-0 (4-chlorophenyl) ethenyl] -1,2,3,6-tetrahydronitrogen [4,5-bH 丨Ethyl-5-carboxylic acid ethyl ester; MS (ES): 409 (MH +); 85585 -236- 200307684 3- (4-chloromethylbenzyl) 1,2,3,6_tetrahydroazepine Ethyl [4,5 hepta] oxindole-5-carboxylic acid ethyl ester; MS (ES): 409 (MH +); 3- (3-chloromethylbenzyl) -1,2,3,6- Tetrahydronitrogen is benzo [4,5_b] pyridin-5-carboxylic acid ethyl ester; MS (ES): 409 (MH +); 3- (2-fluoren-2-yl-ethylfluorenyl) -1,2 , 3,6-tetrahydronitropyrene [4,5-b: KI indole-5-carboxylic acid ethyl ester; MS (ES): 381 (MH +); 1,6-dihydro-2H-nitropyrene [ 4,5 hepta] 3-Benzyl-3,5-dicarboxylic acid 3-benzyl ester; 5-ethyl ester; MS (ES): 391 (MH +); 3- (2-phenylcyclopropanecarbonyl) -1,2 , 3,6_tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES): 401 (MH +); 3- (4-Aminosulfonylbenzyl) ) -l, 2,3,6-tetrahydronitrocarbazone [4,5seven] indole-5-carboxylic acid ethyl ester; MS (ES): 440 (MH +); 3 · (3-fluoro-4 -Trifluoromethylbenzoic acid group) -1,2,3,6-tetrahydronitrocarba [4,5-b] 4 | Homo_ 5-carboxylic acid ethyl ester; MS (ES): 447 (MH +) ; 3 · (2-Fluoro-6-trifluoromethylbenzyl) -1,2,3,6-tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid ethyl ester; ; MS (ES): 447 (MH +); 3- (2-Methenylbenzoate) -1,2,3,6-tetrahydronitrogen is [4,5-b] 〃5 丨 lar-5- Ethyl methanoate; MS (ES): 439 (MH +); 3 · [2- (4-chlorophenoxy) ethenyl] -1,2,3,6-tetrahydronitrogen [4, 5-b] ethyl indole-5-metanoate; MS (ES): 425 (MH +); 3- [3- (3-trifluoromethylphenyl) acrylfluorenyl] · 1,2,3, 6-tetrahydronitrogenates [4,5-b] Wh-5-carboxylic acid ethyl ester; MS (ES): 455 (MH +); 3- (3-ethoxypropylpropyl) -1, 2,3,6_tetrahydronitrocarba [4,5Hepta] indolin-5-carboxylic acid ethyl ester; MS (ES): 385 (MH +); 85585 -237- 200307684 3- (2-acetamidine Phenyl-2-phenylethyl ethynyl) -1,2,3,6 · tetrahydronitrogen deuterates [4,5-13] 1 ^ 丨 Homo-5-carboxylic acid ethyl ester; MS (ES): 433 (ΜΗ +); 0 3- (2-Ethoxyfluorethenyl) -1,2,3,6-tetrahydronitrogeno [4,5 七] 4 丨 Ethyl-5-carboxylic acid ethyl ester; MS ( ES): 357 (MH +); 3- (4 · butoxybenzyl) · 1,2,3,6 · tetrahydronitrogen [4,5 七] Ethyl indole-5-carboxylic acid; MS (ES): 433 (MH +); 3- (methyl (phenyl) aminomethylamidino) -1,2,3,6-tetrahydronitrogen [4] , 5VII] Methyl indole-5-carboxylic acid; MS (ES): 390 (MH +); φ 3- (2-chloro_2,2-diphenylethyl) -1,2,3 , 6-Tetrahydronitrogeno [4,5-b] H 丨 Homo-5-carboxylic acid ethyl ester; MS (ES): 485 (MH +); 3- (2-Methoxy-2-phenylethyl) (Methenyl) · 1,2,3,6-tetrahydronitrocarbazone [4,5Hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 419 (ΜΗ +); 3- (5_fluoro Phenyl-2-trifluoromethylbenzylidene) -1,2,3,6-tetrahydronitrocarba [4,5-b; ethyl n-do-5-carboxylic acid; MS (ES): 447 (MH +); 3- (4-Butylbenzylidene) -1,2,3,6-tetraazanitrogeno [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES ): 417 (ΜΗ +); φ 3- (6-airpyridine-3-carbonyl) -1,2,3,6-tetrahydronitrogen is eh [4,5hepta] indole-5-carboxylic acid ethyl ester ; MS (ES): 396 (MH +); 3- (3 · Dichloromethylbenzyl) · 1,2,3,6-tetrahydronitrazol [4,5-b] Kordole-5 -Ethyl carboxylic acid; MS (ES): 443 (MH +); 3- (4-pentylbenzyl) -1,2,3,6-tetrahydronitrogen [4,5 七] wormworm indole Ethyl-5-carboxylic acid; MS (ES): 431 (MH +); 3- (3-phenylpropenylfluorenyl) -1,2,3,6-tetrahydronitrogen Phyto [4,5-Chong 5′-indole-5-carboxylic acid ethyl ester; MS (ES): 387 (MH +); 85585 -238- 200307684 3-diethylaminemethylmethyl-1,2,3, 6_Tetrahydronitrogeno [4,5-b] e 丨 Homo-5-carboxylic acid ethyl ester; MS (ES): 356 (MH +); 3- (2-Acetylidene) -l, 2 , 3,6-Tetrahydronitrogen is inducing [4,5 七] 4 丨 Homo-5-acrylic acid ethyl ester; MS (ES): 487 (MH +); 3-diphenylethylfluorenyl-1,2, 3,6-tetrahydronitrogen appeals to [4,5-b] W 丨 Hydroxy-5-acrylic acid; g (MS): 451 (MH +); 3_ (4,7,7-King methyl-3- Keto-2_oxobicyclo [2.2.1] heptane small carbonyl group) 1,2,3,6-tetrahydronitrogeno [4,5-b] 4 indole-5-carboxylic acid ethyl ester; MS (ES): 437 (MH +); 3- (4 • trifluoromethoxybenzyl) 1,2,3,6-tetrahydronitrogeno [4,5_b] indole-5_carboxylic acid ethyl ester ; MS (ES): 445 (ΜΗ +); 3 · methylmethylbenzo-2-carbonyl) -1,2,3,6-tetrahydronitrogeno [4,5-bH 丨 indole-5 -Acidic acid ethyl ester; MS (ES): 415 (MH +); 3- (4-phenylazophenylbenzyl) _1,2,3,6-tetrahydronitrogen [4,5 七] Methyl indole-5-carboxylic acid; MS (ES): 465 (MH +); 3_ (3_bromobenzyl) -1,2,3,6-tetrahydronitrogen [4,5 -b] W--5--5-ethyl acetate; MS (ES): 439 (MH +); 3- (4_third -Butylbenzylidene) -l, 2,3,6-tetrahydronitrogeno [4,5 七] # 丨 indole-5_carboxylic acid ethyl ester; MS (ES): 417 (MH +); 3 -(2-methoxybenzylidene) -1,2,3,6_tetrahydronitrocarba [[4,5Hepta] indole-5-acetic acid ethyl ester; MS (ES): 391 (MH +) ; 3- (4-Fluoro-3-trimethylbenzylidene) -l, 2,3,6-tetrahydronitrocarba [4,5-b] 4 丨 Ethyl-5-carboxylic acid ethyl ester ; MS (ES) ·· 447 (MH +); 3-propanyl-1,2,3,6-tetrahydronitrogen [4,5H &gt;?] indole-5_carboxylic acid ethyl ester; MS (ES): 311 (MH +); 85585 -239- 200307684 3- (3-cyanobenzylidene) -l, 2,3,6-tetrahydronitrogen is [4,5Hepta] indole- Ethyl 5-carboxylate; MS (ES): 386 (MH +); 3 · (3,4-dichlorobenzyl) -l, 2,3,6-tetracarbazine [4,5- b] W 丨 Homo-5-acrylic acid ethyl ester; MS (ES): 429 (MH +); 3- (4-methoxycarbonylbutylfluorenyl) -l, 2,3,6-tetrahydronitrogen [4, 5 Hepta] oxindole-5-carboxylic acid ethyl ester; MS (ES): 385 (MH +); 3- (2-ethylhexylfluorenyl) -1,2,3,6 · tetrahydronitrogen [4] , 5-b] indole-5-carboxylic acid ethyl ester; MS (ES): 383 (MH +); 3- (2,6_dichlorobenzyl) -1,2,3,6 · tetrahydro Nitrogen benzo [4,5_bH 丨 indole-5-carboxylic acid ethyl ester; MS (ES): 429 (MH +); 3- (fluoren-1-carbonyl -l, 2,3,6-tetrahydronitrocarbazone [4,5Hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 411 (MH +); 3- (2 • fluoro-3- Trifluoromethyl benzamidine) -1,2,3,6_tetrahydroazepine [4,5-b] indole · 5-carboxylic acid ethyl ester; MS (ES): 447 (MH +); 3- (3-Fluoro-5-trifluoromethylbenzylidene) -1,2,3,6-tetrahydronitrocarba [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES): 447 (MH +); 3- (4-fluoro-2-trifluoromethylbenzyl) -1,2,3,6-tetrahydronitrogen [4,5-b] Indole · 5-carboxylic acid ethyl ester; MS (ES): 447 (MH +); 3- (2-fluoro-4-trifluoromethylbenzyl) -1,2,3,6-tetrahydro Nitrogen [4,5-b] indole · 5 · carboxylic acid ethyl ester; MS (ES): 447 (MH +); 3- (2 · Ethyloxybenzyl) -1,2,3 , 6-Tetrahydronitrocarbazone [4,5Hepta] -5-Ethylcarboxylate; MS (ES): 419 (MH +); 3- (2-Ethyloxy-2-methylpropionamidine ) -1,2,3,6-tetrahydroazepine [4,5 hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 385 (MH +); 85585 -240- 200307684 3- ( 3,5,5-trimethylhexanoic acid group) -1,2,3,6 · tetrahydronitrogeno [4,5_b] Homo-5-carboxylic acid ethyl ester; MS (ES): 397 (MH + ); 3- [2- (4-chlorophenoxy) -pyridine-3-carbonyl] -1,2,3,6-tetrahydroazepine [4,5hepta] indene -5-Ethyl acetate; MS (ES): 488 (MH +); 3- (2 · fluoren-1-ylethylfluorenyl) -1,2,3,6-tetrahydronitrogen [4,5 Hepta] oxindole-5-carboxylic acid ethyl ester; MS (ES): 425 (MH +); 3- (2,4,5_trifluoro-3-methoxybenzyl) -l, 2,3,6 -Tetrahydronitrogeno [4,5-b] earmidine-5-carboxylic acid ethyl ester; MS (ES): 445 (MH +); 3- (2,5-dichloropyrimidine-3-carbonyl) -1,2,3,6-Tetrahydronitrogen benzo [4,5-b] methyl indole-5-carboxylic acid ethyl ester; MS (ES): 435 (MH +); 3- (2H- 咣 晞 _3 _Carbonyl) -1,2,3,6 · tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES): 415 (MH +); 3- (furan-3 · Carbonyl) -1,2,3,6 · Tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES): 351 (MH +); 3-0 thiophene- 3-carbonyl) _1,2,3,6_tetrahydronitrogeno [4,5-b] oxindole-5-carboxylic acid ethyl ester; MS (ES): 367 (MH +); # 3- (2, Dithiophenyl-5-carbonyl) -1,2,3,6-tetrahydronitrogeno [4,5_b] oxindole-5-carboxylic acid ethyl ester; MS (ES): 449 (MH +); 3- (2,3-dihydrobenzofuran-5-carbonyl) -1,2,3,6-tetrahydronitrogeno [4,5_order 5 丨 indole-5-carboxylic acid ethyl ester; MS oES) : 403 (MH +); 3- (2,3-dihydrobenzo [1,4] dioxolene-6-carbonyl) -1,2,3,6-tetrahydronitrogen [4,5Hepta] ethyl indole-5-carboxylic acid; MS (ES): 419 (MH +); 3_ (2_fluorenyl-5-third-butyl_2H-pyridine-3-guan Group) _1,2,3,6_tetrazol ML is eno [4,5-bH 丨 indol_5 · carboxylic acid ethyl ester; MS (ES): 497 (MH +); 85585 -241- 200307684 3_ (3, 4_Xylylenemethyl) -1,2,3,6 · tetrahydronitrogen is eh [4,5_b] indole-5_carboxylic acid ethyl ester; MS (ES): 389 (MH +); 3- [ 3_ (4-trifluoromethoxyphenyl) -propanthionyl] -1,2,3,6-tetrahydronitro p-benzo [4,5-b] p5 indole-5-carboxylic acid ethyl ester; MS (ES): 471 (MH +); 3- (2,3-Xylylenemethyl) -1,2,3,6-tetrahydronitrogeno [4,5-b] indole · 5-carboxyl Ethyl Ester; MS (ES): 389 (ΜΗ +); 3- (2-chloropyridine-4-carbonyl) -1,2,3,6 · tetrahydronitrogeno [4,5-b] indole Ethyl-5-carboxylate; MS (ES): 396 (MH +); 3- (2,6-difluoro-3-nitrobenzylidene) -l, 2,3,6-tetrahydroazepine And [4,5-b: H 丨 indole-5-carboxylic acid ethyl ester; MS (ES) ·· 442 (MH +); 3- (2-methyl-3-phenylpropionyl) -1, 2,3,6-tetrahydronitrocarba [4,5-b] e 丨 indole-5 · carboxylic acid ethyl ester; MS (ES): 401 (MH +); 3- [1- (4 · trifluoromethyl) Pyrimidine_2_yl) _hexahydropyridine-4-carbonyl] -1,2,3,6_tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid Ethyl ester; MS (ES): 514 (MH +); 3- [2- (4-chlorophenoxy) -2-methylpropanyl] -1,2,3,6-tetrahydronitrogen [4,5 VII] Ethyl-5-carboxylic acid ethyl ester; MS (ES): 453 (MH +); 3- (2-chloro-6-methoxy-rhodium-4-yl) _1, 2,3,6_tetrahydronitrogen benzo [4,5-b] p5 | Hydroxyethyl 5-carboxylate; MS (ES): 426 (MH +); 3- [1_ (4-chlorophenyl) -5-propyl-1H_pyrazole-4-carbonyl] · 1,2,3,6-tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES) ·· 503 (ΜΗ +); 3- (5-chloro-4-methoxypyrimidine-3-carbonyl) -1,2,3,6-tetrahydronitrogeno [4,5-b] ^ Ethyl indole-5-carboxylic acid; MS (ES): 431 (MH +); 3- (5-phenyl- [1,3,4] fluorenediazole-2-carbonyl) -1,2,3,6 -Tetrahydronitrogeno [4,5Hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 429 (MH +); 85585 -242- 200307684 3- (2-tert-butyl-5- Methyl_2H_pyrazole-3_carbonyl) -1,2,3,6-tetrahydronitrogeno [4,5_ b; N indole-5 · carboxylate; MS (ES): 421 (MH + ); 3- (Benzo [1,2,5] pyrimidazole-5-carbonyl) 1,2,3,6-tetrahydronitrogeno [4,5_b] indole-5-carboxylic acid ethyl ester ; MS (ES) ·· 419 (MH +); 3- (4-pyrazol-1-ylbenzyl) -l, 2,3,6-tetrahydronitrogen [4,5Hepta] indole -5- rebellion Ethyl ester; MS (ES): 427 (MH +); 3- (2-propylthiopyridine-3-carbonyl) -1,2,3,6-tetrahydronitrogen [4,5-b] ind Indole-5_carboxylic acid ethyl ester; MS (ES) · 436 (MH +); Lu 3- (2-fluorene · 2_ylpyrazole_4_carbonyl) -1,2,3,6_tetrahydro Nitrogen [4,5 hepta] oxindole-5-carboxylic acid ethyl ester; MS (ES): 450 (ΜΗ +); 3- (6-phenoxypyridine-3-carbonyl) -1,2,3 , 6-Tetrahydronitropyrene [4,5Seven &gt;? 丨 Indole-5 · carboxylic acid ethyl ester; MS (ES): 454 (MH +); 3- (5-phenyloxazole-4-carbonyl) · 1,2,3,6_tetrahydronitrozine [4,5-b] oxindole-5-carboxylic acid ethyl ester; MS (ES): 428 (MH +); 3- (4,6-dichloro -1H-pyridol · 2-carbonyl) 1,2,3,6_tetrahydronitrogeno [4,5-b] indole-5_carboxylic acid ethyl ester; MS (ES) ·· 468 (MH +) # 3- (1-methyl_1H-benzotriazole-5-carbonyl) -1,2,3,6-tetrahydroazepine [4,5hepta] indole-5-carboxylic acid ethyl ester ; MS (ES): 416 (MH +); 3_ (quinoxaline-6-carbonyl) · 1,2,3,6-tetrahydronitrogen is inferred with [4,5_b] earthol-5_carboxylic acid ethyl ester MS (ES): 413 (MH +); 3- (5-phenylpyrimin-2-carbonyl) -1,2,3,6-tetrahydronitrogeno [4,5_b] oxindole-5-carboxylic acid ethyl Esters; MS (ES): 443 (MH +); 3- (6-Morpholin_4_ylρ Bidian-3 · Tanji) -1,2,3,6-tetranitroazine Ethyl [4,5-b] 1 ^ 丨 Homo-5-carboxylic acid ethyl ester; MS (ES): 447 (MH +); 85585 -243- 200307684 3- (4-pyrimphen-2-ylbenzidine Yl) 1,2,3,6_tetrahydronitrogeno [4,5-b] oxindole 5-carboxylic acid ethyl ester; MS (ES): 443 (MH +); 3_ (2_phenylpyrazole -4-carbonyl) · 1,2,3,6-tetrahydronitrocarbazone [4,5-b] Ethyl-5-carboxylate; MS (ES): 444 (MH +); 3 · (4 _Fluorenyl-2-pyridine_2_ylpyrazole_5 · carbonyl) -1,2,3,6-tetrahydronitrocarba [4,5hepta] indole · 5-carboxylic acid ethyl ester; MS (ES) ·· 460 (MH +); 3- (2-phenyl-2H-pyrazole-3-carbonyl) -l, 2,3,6-tetrahydronitrogen [4,5-b] indole Ethyl 5-carboxylic acid; MS (ES): 427 (ΜΗ +); 3- (2-phenylsulfanyl p ratio lake-thryl) -1,2,3,6_tetrachloroazepine Benzo [4,5-b] p5 丨 Homo-5-acrylic acid ethyl ester; MS (ES): 470 (MH +); 3- (2-p-tolyloxypyridine-3-carbonyl) -1,2, 3,6-Tetrahydronitrogeno [4,5Hepta] indole-5 · carboxylic acid ethyl ester; MS (ES): 468 (MH +); 3- [5- (2-methylpyrazolyl) -Isoxazole_3_carbonyl] -1,2,3,6-tetrahydronitropyridine [4,5Hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 449 (MH +); 3 -(5-bromo-p-Hydro-3-carbonyl) -1,2,3,6-tetrahydronitrogen is inducing [4,5-b] indoma-5_etherate; MS ( ES): 440 (MH +); 3- [3 · (5 · ethyl- [l, 3,4] -p dijun-2-yl) -phenylpentamidyl] _1,2,3,6_ Tetrahydronitrogero [4,5Heptazone; Ethyl-Indole-5-carboxylic acid ethyl ester; MS (ES): 479 (MH +); 3_ [4- (3 · Three Gas Methyl Ejunyl) Benzyl Fluorenyl] -1,2,3,6-tetrahydroazepine [4,5-b] ethyl indole-5-carboxylic acid; MS (ES): 495 (MH +); 3- (5,3 '_Dimethyl- [3,5 &gt; bisisoxazolyl-4'-carbonyl) -1,2,3,6-tetrahydronitrogen indeno [4,5VII] 4 indole-5-carboxylic acid Ethyl ester; MS (ES): 447 (MH +); 3- [2- (4-chlorophenylthio)? Biyodo-3-yl] -1,2,3,6-tetrahydronitrogen [4,5 七] 4 丨 Ethyl-5-carboxylic acid ethyl ester; MS (ES): 504 (MH +); 85585 -244- 200307684 3- (2-phenoxypyridine-3-carbonyl) -1,2 , 3,6-Tetrahydronitropyrene [4,5Hepta] keyole-5-carboxylic acid ethyl ester; MS (ES) · 454 (MH +); 3- [3-Gas-4- (propane- 2-sulfofluorenyl) pyrimidine-2-carbonyl] -1,2,3,6-tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES) ·· 507 (MH +); 3_ [5_ (4 · chlorophenyl) -2-methylfuran-3-carbonyl] -1,2,3,6-tetrahydronitrogeno [4,5hepta] indole-5 · Ethyl methanoate; MS (ES): 475 (MH +); 3- (2-p-tolylthiopyridine-3-carbonyl) -1,2,3,6-tetra Hydrogen and nitrogen enzymatic [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES) ·· 484 (MH +); φ 3- (2,5-dichloropyridine-3-carbonyl) _1, 2,3,6_tetrahydronitrazol [4,5-b] 4indole-5-carboxylic acid ethyl ester; MS (ES): 430 (MH +); 3_ (5 · Third-butyl_2_formaldehyde Furan-3-carbonyl) -1,2,3,6-tetrahydronitrogeno [4,5-b] oxindole-5-carboxylic acid ethyl ester; MS (ES): 421 (MH +); 3 -[1_ (4-methoxyphenyl) · 5-methyl-1H-pyrazole-4-carbonyl] -1,2,3,6-tetrahydronitrogeno [4,5Hepta] indole- Ethyl 5-carboxylate; MS (ES): 471 (MH +); 3- (5-ρ Bi-Yodo-2-ylρ-sepene-2-yl) -1,2,3,6-tetraazanitrogen Epi [4,5VII] 〃5 丨 Homo-5-chinoic acid ethyl ester; MS (ES): 444 (MH +); φ 3 · (5 · methyl-3-phenylisoxazole · 4carbonyl) -1,2,3,6-tetrahydronitrocarba [4,5Hepta] ardol · 5-carboxylic acid ethyl ester; MS (ES): 442 (ΜΗ +); 3- (5-methyl small benzene -1H-pyrazole-4-carbonyl) -1,2,3,6 · tetrahydronitropyro [4,5 hepta] oxindole-5-carboxylic acid ethyl ester; MS (ES): 441 (MH +) ; 3- (4-methyl-2-phenylthiazole · 5-carbonyl) · 1,2,3,6-tetrahydronitrogeno [4,5-b &gt; 5 丨 indole · 5-carboxylic acid ethyl ester ; MS (ES) ·· 458 (ΜΗ +); 3- (1,3_dimethyl-1H-quinone [2,3-c] 外 b 峻 _5_ 黢 基) _ 1,2,3,6-Tetrahydronitrogen benzo [4,5-b] W indole-5 · carboxylate; MS (ES): 435 (MH +); 85585 -245- 200307684 3- (benzo [b] Pyrimidine_3_carbonyl) -1,2,3,6-tetrahydronitropyrene [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES): 417 (MH +) ; 3- (3-methyl-5-phenylisoxazole_4-carbonyl) -l, 2,3,6-tetrahydronitrogeno [4,5hepta] oxindole 5-carboxylic acid ethyl ester ; MS (ES): 442 (MH +); 3- (3,4_dihydro_2H-benzo [b] [l, 4] dioxazepine-7-carbonyl) -1,2,3 , 6-Tetrahydronitrobenzyl [4,5Hepta] indole-5_carboxylic acid ethyl ester; MS (ES): 433 (MH +); 3- (5-methyl_2_phenyl-2H_ [1 ， 2,3] · triazole_4-carbonyl） -1,2,3,6-tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES): 442 (MH +); φ 3- (2-methyl-5-phenylfuran-3-carbonyl) -1,2,3,6-tetrahydronitrogen [4,5-b] indole-5-carboxy Ethyl Ester; MS (ES): 441 (MH +); 3- (5-thiophen-2-ylpyridine_3_carbonyl) · 1,2,3,6-tetrahydronitropyrene [4,5-b ] Etholin-5-carboxylic acid ethyl ester; MS (ES): 444 (MH +); 3- (3-methylbutylfluorenyl) -1,2,3,6-tetrahydronitrogen [4,5 七] 4 indole-5-carboxylic acid ethyl ester;

MS (ES): 341 (MH +); X 3- (3,3-dimethylbutylfluorenyl) -l, 2,3,6-tetrahydronitrogeno [4,5-b] indole-5-carboxy Ethyl Ester; MS (ES): 355 (MH +); # 3 · Isobutyridyl-1,2,3,6-tetrahydronitrocarba [4,5Hepta] indole-5-Arenyl Ester; MS (ES): 327 (MH +); 3-butylfluorenyl-1,2,3,6 · tetrahydronitrogeno [4,5-b; N-do-5_carboxylic acid ethyl ester; MS (ES): 327 ( MH +); 3 · (2,2 · Dimethylpropionyl) · 1,2,3,6-tetrahydronitrogen is benzo [4,5-b] indole-5-carboxylic acid ethyl ester; MS ( ES) ·· 341 (MH +); 3_ (3-chloro-2,2-dimethylpropanyl) -l, 2,3,6-tetrahydronitrogen [4,5-b] W 丨Homo_5-carboxylic acid ethyl ester; MS (ES): 375 (MH +); 85585 -246- 200307684 3- (2-chloropropylamido) -1,2,3,6-tetrahydronitrogen [ 4,5-1 ^ 5 丨 Ethyl-5-carboxylic acid ethyl ester; MS (ES): 347 (MH +); 3_ (Jin Gang Shao-1-Wei Ji) _1, 2, 3, 6-tetrahydronitrogen Ethyl [4,5-b] p5 ethyl_5-chitoate; MS (ES): 419 (MH +); 3. · Dimethylaminomethylmethyl-1,2,3,6-tetrahydronitro Homo [4,5 hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 328 (MH +); 3- (2,4,6-trimethylbenzyl) -1,2, 3,6-Tetrahydronitrogeno [4,5Hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 403 (MH +); 3- (4-Chloro-3-nitrobenzylidene) -1,2,3,6 · tetrahydronitrogeno [4,5hepta] indole-5-carboxylic acid ethyl ester ; MS (ES): 440 (ΜΗ +); and 3- (Methylpyridin-3-fluorenyl group) 1,2,3,6-tetrahydronitrogen [[4,5 七]] 啕 -5- Ethyl methanoate; MS (ES): 362 (MH +). Example 72 3- (4-methyl-3_nitrobenzenesulfonyl) -l, 2,3,6-tetrahydronitrogen [4] , 5-B] &lt; Preparation of indole-5_ ethyl acidate;

A. The title compound was used in a manner analogous to that described in Example 71, using 2-hydroxymethyl-1,2,3,6_tetrahydronitrogen to en [4,5-1); Ethyl chloride and 4-methyl_3_ 85585 -247- 200307684 Nitrobenzenesulfonium (~ 3.4 halo); Ms (ES): 456 (MH +) B. The following compounds are used in this way, using Properly substituted sulfonium sulfonium is made from: 3- (3,5-dimethylisoxazolylsulfonylsulfonyl) 4,2,3,6-tetrahydronitrogen [[4,5 七]] -5_ carboxylic acid ethyl ester; MS (ES): 416 (MH +). H2-cyanobenzenesulfonyl) -i, 2,3,6-tetrahydronitrogeno [4,5heptadol_5 _Ethyl carboxylate; MS (ES): 422 (MH +); M3-chloro-2-toluenesulfonyl) _1,2,3,6-tetrahydronitrogen is [4,5-b] zindole Ethyl-5-carboxylic acid; MS (ES): 445 (MH +); 3- (4-Butylphenylenyl) -i, 2,3,6-tetrahydronitrogen [4,5 七] 4-Ethyl-5-carboxylic acid ethyl ester; MS (ES): 453 (MH +); M4-methyl-3_nitrobenzenesulfonyl) -methyl, 2,3,6_tetrahydronitrogen [4, 5-bH indole-5-carboxylic acid ethyl ester; 456 (MH +); 3- (biphenyl-4-sulfofluorenyl) 1,2,3,6_tetrahydronitrogen [4,5secondary? 丨Ethyl indole-5-chinoate; MS (ES): 473 (MH +); 3- (2,5-dichlorobenzenesulfonyl) -l, 2,3,6 -Tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES): 465 (MH +); 3- (3,5-dimethylisoxazole-4-sulfonate Fluorenyl H, 2,3,6-tetrahydronitrogen is engulfing [4,5 handsome? 丨 Homo-5-Ethyl Acetate; MS (ES): 416 (MH +); 3- (2-Daidong] Buy an acid group) 1,2,3,6-tetrahydronitrogen benzo [4,5_b] P5 丨 Homo-5-acrylic acid ethyl ester; MS (ES): 422 (MH +); 3- (3-chloro 2-tolylsulfonyl) -1,2,3,6-tetrahydronitrogeno [4,5 hepta] oxindole-5-carboxylic acid ethyl ester; MS (ES): 445 (MH +); 3 -(4-butyl winter% acid group) -l, 2,3,6-tetra-mouse breech 丨 no-5-carboxylic acid ethyl ester 85585 -248- 200307684; MS (ES): 453 (MH +); 3- (4-methyl-3-nitrobenzenesulfonyl) -l, 2,3,6-tetrahydronitrocarba [4,5Hepta] Homo-5-acrylic acid ethyl ester; MS (ES ): 456 (MH +); 3_ (biphenyl-4-sulfofluorenyl) -1,2,3,6-tetrahydronitrogeno [4,5hepta] oxindole-5-carboxylic acid ethyl ester; MS (ES): 473 (MH +); and 3- (2,5-dichlorobenzenesulfonyl) -1,2,3,6-tetrahydronitrogen [[4,5Hepta]] indole-5-carboxyl Ethyl Ester; MS (ES): 465 (MH +) · Example 73 φ 3- (4-n-butoxycarbonyl-anilinemethyl) · 1,2,3,6 · Tetrahydronitrogen benzo [4 , 5-Β] ^ Dole · 5-carboxylic acid ethyl ester preparation

A. The title compound was prepared in a manner similar to that described in Example 72, using ethyl 2-hydroxymethyl-1,2,3,6-tetrahydroazepine [4,5hepta] indole-5-carboxylic acid ethyl ester. Made with 4- (butoxycarbonyl) phenyl isocyanate (~ 2.0 mg); Ms (ES): 476 (ΜΗ +) · B · The following compounds are made in this way using appropriately substituted isocyanates: 3- (2-Fluoro-5-difluoromethylbenzylamidomethylhydrazinetetrahydronitrocarbazone [4,5Hepta] indoma-5-metanoic acid ethyl ester; MS (ES): 462 (MH +); 3_ (2 ^ ylaniline methyl alcohol) _U3,6-tetrahydronitrocarba [4,5seven] indole-5-carboxylic acid ethyl 85585 -249- 200307684 ester; MS (ES): 466 (MH +); 3- (3-Fluorobenzylamine formamidine) -1,2,3,6-tetrahydronitrocarba [4,5hepta] oxindole-5-carboxylic acid ethyl ester; MS (ES): 408 (MH +); 3- (2-Bromophenylaminomethylamidino) -1,2,3,6-tetrahydronitrocarba [4,5-b; N-dole-5-carboxylic acid ethyl ester; MS ( ES): 454 (MH +); 3- (3_phenoxyaniline methylol) · 1,2,3,6-tetrahydronitrocarba [4,5Hepta] oxindole-5-carboxylic acid ethyl ester ; MS (ES): 468 (ΜΗ +); 3- (2,4-dichlorobenzylaminemethylamidino) _1,2,3,6_tetrahydronitrogen is [4,5 七] Ethyl 5-carboxylate; MS (ES): 458 (ΜΗ +); 3- (4-butoxyfluorenyl Aniline) 1,2,3,6_tetrahydronitrogen deuterates ethyl [4,5-b] p? Budol-5-metanoate; MS (ES): 476 (MH +); 3- ( 2,3-dihydrobenzo [1,4] dioxolene-6-ylaminomethylmethyl) -1,2,3,6-tetrahydronitrogeno [4,5-bH 丨 indole- Ethyl 5-carboxylic acid; MS (ES): 434 (MH +); 3- (4-methylthioaniline formamidine) 1,2,3,6-tetrahydronitrogen [4,5 七] Indole-5-carboxylic acid ethyl ester; MS (ES): 422 (MH +); 3- (3,4-dimethoxyanilinemethyl) -1,2,3,6-tetrahydronitrogen [4,5 Hepta] oxindole-5-carboxylic acid ethyl ester; MS (ES): 436 (MH +); 3- (2,5-monomethylaspartylmethyl) -1,2,3,6 -Tetrakis-nitrogen p-benzo [4,5-b] 1 ^ 丨 Homo-5-chinoic acid ethyl ester; MS (ES): 404 (MH +); 3- (3-cyclopentyloxy-4-methoxy Phenylamine formamyl) ^ 2,3,6-tetrahydronitrogeno [4,5-b] indolecarboxylic acid ethyl ester; MS (ES): 490 (MH +); 3- (2-chloroethyl Methylaminomethyl) -1,2,3,6-tetrahydronitrogen deuterates [4,5 hepta] oxindole I carboxylic acid ethyl ester; MS (ES): 362 (MH +); 3- (4-methyl) Benzo [aminoformyl] -1,2,3,6_tetrahydronitrocarba [4,5hepta] pyridin-5-carboxylic acid 85585 -250- 200307684 ethyl ester; MS (ES): 404 (MH + ); 3- (2 • propylanilinemethyl) -l, 2,3,6-tetrahydronitrogen [4,5 Seven] 4 丨 Ethyl 5-carboxylate; MS (ES): 418 (MH +); 3- (2-ethyl-6-methylanilinemethyl) 1,2,3,6-tetrahydro Nitrogen [4,5-b] whistle_5 · carboxylic acid ethyl ester; MS (ES): 418 (ΜΗ +); 3- (3-methylbenzylamine formamyl) 1,2,3 , 6-Tetrahydronitrobenzyl [4,5Hepta] pyrene-5_metanoate ethyl ester; MS (ES): 404 (MH +); 3- (2-methylamidomethylformamyl) -1, 2,3,6-tetrahydronitrogen appeals to [4,5Hepta] indino-5_chinoic acid ethyl ester; MS (ES): 404 (MH +); 3- (2-chlorophenylamine methyl alcohol) -l, 2,3,6-tetrahydronitrogen appeals to [4,5 七] 4 丨 -5-5 carboxylic acid ethyl ester; MS (ES) · 410 (MH +); 3- (2,3,4 -Trifluoroaniline formamyl) -1,2,3,6-tetrahydronitrocarba [4,5Hepta] indo-5-acrylic acid ethyl ester; MS (ES): 430 (MH +); 3 -(4-Fluoro-3-trifluoromethylanilinemethyl) 1,2,3,6_tetrahydronitrogeno [4,5Hepta] ethylindole-5-carboxylic acid ethyl ester; MS (ES ): 462 (MH +); 3_Pentaeryl methamido-1,2,3,6 · Four wind nitrogen entrains [4,5 &quot; b] p5 丨 Hou_5_Ethanoate; MS (ES): 466 (MH +); 3- (2_methoxycarbonylanilinemethylamino) _1,2,3,6_tetrahydronitrogen is [4,5 七] 〃5 丨 Noise_5_traiter acid Ethyl ester; MS (ES): 434 (MH +); 3- (3-cyanophenylaminomethylamidino) -1,2,3,6- Tetrahydronitrogero [4,5Hepta] indole-5-acetic acid ethyl ester; MS (ES): 401 (MH +); 3- (diphenylmethylaminomethyl) 1,2,3,6 _Tetrahydronitrogero [4,5Hepta] indoma-5-carboxylic acid ethyl ester; MS (ES): 466 (MH +); 3- (4-fluorophenylaminomethylamidino) -1,2, 3,6-tetrahydronitrile [4,5-b] indo-5-acetic acid ethyl 85585 -251-200307684 ester; MS (ES): 394 (MH +); 3 · (2,4-dimethyl Aniline (methylanilide) -i, 2,3,6-tetrahydronitrocarba [4,5-b: Hindole-5-carboxylic acid ethyl ester; MS (ES): 404 (MH +); 3- ( 4-methoxybenzylamine formamyl) -i, 2,3,6-tetrahydronitrogeno [4,5hepta] oxindole-5-carboxylic acid ethyl ester; MS (ES): 420 (MH + ); 3- (2-Chloro-4-trifluoromethylanilinemethyl) -i, 2,3,6-tetrahydronitrogeno [4,5Hepta] 4 indole-5 · carboxylic acid ethyl ester ; MS (ES): 478 (MH +); 3- (2-phenoxyaniline methylamino) -1,2,3,6-tetrahydronitrazol [4,5-b] 4 丨 lar-5 -Ethyl methanoate; MS (ES): 468 (MH +); 3- (4-methoxy-2-tolylaminemethylamidino) -1,2,3,6-tetrahydronitrogen [4] , 5-Chong 5 丨 Indole-5-carboxylic acid ethyl ester; MS (ES) ·· 420 (MH +); 3-Anilinomethyl-1,2,3,6-tetrahydronitrogen [4,5 -b] ethyl indole-5-carboxylic acid; MS (ES): 376 (MH +); 3- (3-chloro -2-Methylaniline methylamidino) -1,2,3,6-tetrahydronitrocarbazone [4,5-b] Homo-5-carboxylic acid ethyl ester; MS (ES): 424 (MH +) ; 3- (2-trifluoromethylanilinemethyl) 1,2,3,6_tetrahydronitrogen deuterates [4,5-b] W 丨 Homo-5-acrylic acid ethyl ester; MS (ES ): 444 (MH +); 3-p-tolylaminomethylamido-1,2,3,6-tetrahydronitrogeno [4,5_b] g 丨 indole-5-carboxylic acid ethyl ester; MS (ES ): 390 (MH +); 3- (2. Chloroamidomethylamidino) -1,2,3,6-tetrahydronitrogen is eh [4,5Hepta] indole-5-metanoate ethyl ester; MS (ES): 424 (MH +); 3- (4-butoxyaniline methylsilyl) -1,2,3,6-tetrahydronitrocarba [4,5Hepta] indole: ethyl carboxylate ; MS (ES): 448 (MH +); 3- (2,6-monoethylaspartamidinyl) -l, 2,3,6-tetrahydronitrogen p-pine [4,5 七] 4 丨Hou_5 · carboxy85585 -252- 200307684 ethyl acetate; MS (ES): 432 (MH +); 3- (4-isopropylanilinemethyl) -1,2,3,6_tetrahydronitrile Ethyl [4,5 hepta] oxindole-5-carboxylic acid ethyl ester; MS (ES): 418 (MH +); 3- (3-trifluoromethyl-anilinemethyl) -1,2,3,6 _Tetrahydronitrogero [4,5-b] pyridin-5-carboxylic acid ethyl ester; MS (ES): 444 (MH +); 3- (3,5-dimethylanilinemethyl) -1 , 2,3,6-tetrahydronitrogen benzo [4,5-b] Windole-5-carboxylic acid ethyl ester MS (ES): 404 (MH +); 3- (biphenyl-2-ylaminomethylmethyl) 1,2,3,6_tetrahydronitrogeno [4,5Hepta] doline-5 · carboxylic acid Ethyl ester; MS (ES): 452 (MH +); 3- (5-fluoro-2-methylaniline methyl) -l, 2,3,6-tetrachloronitrogen [4,5-b ] 1 ^ 丨 A-5 · ethyl carboxylate; MS (ES) ·· 408 (ΜΗ +); 3_ (3-chloro-4-fluorophenylcarbamate) -1,2,3,6_ Tetrahydronitrogen is benzo [4,5-b] p? BUDO · 5-ethyl carboxylate; MS (ES) · 428 (ΜΗ +); 3_ (2-isopropyl-6-methylaniline ) · 1,2,3,6-Tetrahydronitrogen benzo [4,5-b] # Budor · Ethyl 5-carboxylate; MS (ES): 432 (MH +); 3- (4-phenoxy Aniline (methylanilide) -1,2,3,6-tetracarbazine deuterates [4,5 七] # 丨 Ac-5 · ethyl methanoate; MS (ES): 468 (MH +); 3- ( 2 • methoxyphenylamine methylamidino) -1,2,3,6-tetrahydronitro, and [4J 七] 4 丨 Homo-5-carboxylic acid ethyl ester; MS (ES) ·· 406 (MH +) ; Chloro-5-trifluoromethylanilidemethyl) -l, 2,3,6-tetrahydronitrile; [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES) : 478 (MH +); 3- (1-methoxycarboxy-2_dongylethylaminemethylSi) -1,2,3,6-tetrahydronitrogen indeno [4,5_b] indole_5_ Ethyl carboxylate; MS (ES) ·· 462 (MH +); fluoro-3_difluoromethylaspartamine Formic acid group) · 1,2,3,6-tetrahydronitrile v? Pine [4,5-b] p5 丨 85585 -253-200307684 ethyl indole-5-carboxylic acid; MS (ES): 462 (MH + ); 3- (1-fluoren-1-ylethylaminemethylamidino) -l, 2,3,6-tetrahydronitrogen [4,5_b; H 丨 indole-5-carboxylic acid ethyl ester; MS (ES) ·· 454 (MH +); 3- (fluoren-1-ylaminemethylamidino) -l, 2,3,6-tetrahydronitrogen entrains [4,5 七] Ethyl ester; MS (ES): 426 (MH +); 3- (Hydroxy-5-ylaminomethylmethyl) -1,2,3,6-tetrahydronitrogen [4,5 七],? -5-Leptanoic acid ethyl ester; MS (ES): 416 (MH +); 3-benzylaminomethylamido-1,2,3,6-tetrahydronitrogeno [4,5hepta] indole-5 -Ethyl carboxylate; MS (ES): 390 (MH +); 3_ (3,4_difluorophenylamine methane) -l, 2,3,6-tetrahydronitrogen [4,5_b] 4 丨 Homo-5-acrylic acid ethyl ester; MS (ES): 412 (MH +); 3_ (4-ethylaniline) -1,2,3,6-tetrahydronitrogen [4,5 七] 4 丨 Hang_5_Ethyl Acetate; MS (ES): 404 (MH +); 3- (2,5-Mono-Cyclomethylamine) -1,2,3,6-Tetrachloronitrogen Heiwa [4,5-13] '15 丨 Ethyl-5-carboxylic acid ethyl ester; MS (ES): 412 (MH +); 3_ (3,4_dimethylanilidemethyl) · 1,2, 3,6_Tetrahydronitrogeno [4,5Hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 404 (MH +); 3- (2-fluorophenylamine methylamidino) -1,2,3,6-tetrahydronitrogen [4,5 七] 4 丨 Hou · 5_ Ethyl ester; MS (ES): 394 (ΜΗ +); 3- (4_ethoxyanilinemethyl) -1,2,3,6-tetrahydroazepine [4,5 七] indura-5 _Ethyl Acetate; MS (ES): 420 (ΜΗ +); 3- (3-chloropropylaminomethylamidino) -1,2,3,6-tetrahydronitrogen [4,5_b] Indole-5__ carboxylic acid ethyl ester; MS (ES): 376 (MH +); 3- (2-ethoxycarbonylethylaminemethylamidino) -1,2,3,6-tetrahydronitrogen [ 4,5Seven &gt; 5 丨 V. 5_ 85585 -254- 200307684 Ethyl carboxylate; MS (ES): 400 (MH +); 3- (3-chlorophenylamine methyl) -1,2,3 , 6-Tetrahydronitrogen is infused with [4,5Hepta] Homo-5-acrylic acid ethyl ester; MS (ES): 410 (MH +); 3-pentylaminomethylamidino-1,2,3,6 -Tetrahydronitrogeno [4,5 hepta] indolin-5-chinoic acid ethyl ester; MS (ES): 370 (MH +); 3- (2-isopropylanilinemethyl) -1,2, 3,6-tetrahydronitrile appeals to [4,5 hepta] indole-5-acetic acid ethyl ester; MS (ES): 418 (MH +); 3- (3-ethylamidoanilinemethyl) -l , 2,3,6-Tetrahydronitrogen benzo [4,5 hepta] indano-5-acrylic acid ethyl ester; MS (ES): 418 (MH +); 3 · (3,4-dichlorobenzylamine Formamyl) -l, 2,3,6-tetrahydronitrazine and [4,5_b] indor-5 -Ethyl methanoate; MS (ES): 458 (MH +); 3- (2-fluoro_5_methylanilinemethyl) 1,2,3,6-tetrahydronitrogen is entrained [4,5 7) Ethyloxy-5-carboxylic acid ethyl ester; MS (ES): 408 (MH +); 3- (1-fluoren-1-ylethylaminomethyl) -1,2,3,6-tetrakis Hydrogen and nitrogen appeal to [4,5 七] 1 ^ 丨 -5-Ethyl 5-valerate; MS (ES) · 454 (MH +); 3- (butoxymethylmethylaminomethyl) -l, 2,3,6-tetrahydronitrile appeals to [4,5_b] quinone-5-carboxylic acid ethyl ester; MS (ES): 414 (MH +); 3_ (4_third-butylanilide) -1,2,3,6 · Tetrahydronitrogen deuterates [4,5Hepta] indomo-5-acrylic acid ethyl ester; MS (ES): 432 (MH +); 3- (ethoxycarbonylmethylcarbamic acid) Radical) -1,2,3,6-tetrahydronitro p-benzo [4,5 七] 4 丨 Homo-5-acrylic acid ethyl ester; MS (ES) ·· 386 (MH +); 3- (3 • Methylthioanilinocarboxylic acid) 1,2,3,6_tetrahydroazepine benzo [4,5 hepta] β 丨 Homo-5-acrylic acid ethyl ester; MS (ES): 422 (ΜΗ +); 3- (4-methoxyphenylamine formamidine) -1,2,3,6-tetrahydronitrogen deuterates [4,5_b] indolecarboxylic acid 85585 -255- 200307684 ethyl ester; MS (ES): 406 (MH +); 3 decathiophen-3-ylaminomethylmethyl) 1,2,3,6 · tetrahydronitrogeno [4,5-b] indole-5_carboxylic acid ethyl ester; MS ( ES): 382 (MH +); 3- (3,5. Isoxazolylamine methylamidino) -l, 2,3,6-tetrahydronitropyridine [4,5Hepta] Ethyl indole-5_carboxylate; MS (ES): 395 (MH +); 3- (2-Butoxycarbonylanilinomethyl) 1,2,3,6-tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES): 476 (MH +); 3- (2-Ethylanilidemethyl) 1,2,3,6-tetrahydronitrocarba [4,5Hepta] oxindole-5-carboxylic acid ethyl ester; MS (ES) : 404 (MH +); 3 · (3-ethoxycarbonylanilidemethyl) · 1,2,3,6-tetrahydroazepine [4,5Hepta] indole · 5-carboxylic acid ethyl ester; MS (ES): 448 (ΜΗ +); 3 · Butylaminomethylamido-1,2,3,6-tetrahydronitrocarbazone [4,5Hepta] earmoline-5-carboxylic acid ethyl ester; MS ( ES): 356 (MH +); 3- (4-fluorobenzylamine formamidine) -l, 2,3,6-tetrahydronitrogen [4,5-b] pyridin-5 · carboxylic acid Ethyl ester; MS (ES): 408 (ΜΗ +); 3- (2-Fluoro-6-trifluoromethylaniline methyl) 1,2,3,6_tetrahydroaza-hudoline · 5 · Ethyl methanoate; MS (ES): 462 (ΜΗ +); 3- (3-ethylanilinemethylmethyl) -1,2,3,6-tetrahydronitrogen [4,5 七] adol -5-Ethyl carboxylic acid; MS (ES): 404 (MH +); 3 · m-tolylaminomethylamidino-1,2,3,6-tetrahydronitrogen [4,5Hepta] indole- Ethyl 5-carboxylate; MS (ES): 390 (MH +); 3- (4 • benzylanilinemethyl) -l, 2,3,6-tetrahydronitropyrene [4,5hepta] oxindole-5 · carboxylate; MS (ES): 466 (MH +); 3-Phenethylaminemethylamidino-1,2,3,6-tetrahydronitrocarba [4,5-b] W 丨 Homo-5-carboxylic acid ethyl ester 85585 -256- 200307684; MS (ES) : 404 (MH +); 3- (2-ethoxyphenylamine formamidine) -l, 2,3,6-tetrahydronitrogen deuterates [4,5Hepta] oxindole-5-carboxylic acid ethyl ester; MS (ES): 420 (MH +); 3- (4-trifluoromethylanilinemethyl) · 1,2,3,6 · tetrahydronitrogeno [4,5-bH 丨 indole-5-carboxyl Ethyl Ester; MS (ES): 444 (MH +); 3- (3 · Fluoro-4-methylanilinemethyl) · 1,2,3,6-tetrahydronitrogen is entrained [4,5_bH 丨Indole-5-carboxylic acid ethyl ester; MS (ES): 408 (MH +); 3- (biphenyl-4-ylaminomethylamidino) -1,2,3,6 · tetrahydroazepine [4, 5Seven] oxindole-5_carboxylic acid ethyl ester; MS (ES): 452 (MH +); 3- (2,6-difluorophenylaminomethylamidino) -1,2,3,6-tetrahydro Nitrogen p-benzo [4,5-b] 4 丨 Homo-5-carboxylic acid ethyl ester; MS (ES): 412 (MH +); 3 · (4-ethoxycarbonylanilinemethyl) -1,2, 3,6-Tetrahydronitrogeno [4,5Hepta] indole-5 · carboxylic acid ethyl ester; MS (ES): 448 (ΜΗ +); 3- (3-chloro-4-methylaniline Fluorenyl) _1,2,3,6_tetrahydronitrogens [4,5-b] b? 卜Dota-5-carboxylic acid ethyl ester; MS (ES): 424 (MH +); 3- (2,5-dimethoxyaniline carboxylic acid) -1,2,3,6_tetrahydronitrogen carb [4 , 5_b] K 丨 Homo-5-carboxylic acid ethyl ester; MS (ES): 436 (MH +); 3- (3,5-dichlorophenylaminemethylmethyl) · 1,2,3,6-tetrakis Hydrogen-nitrogen enzymatic [4,5 hepta] β 丨 Homo-5-chinoic acid ethyl ester; MS (ES): 444 (ΜΗ +); 3- (2-Third-butyl-6-methylaniline formamidine Group) 1,2,3,6-tetrahydronitrogen benzo [4,5,5,5,5-indol-5-carboxylic acid ethyl ester; MS (ES): 446 (ΜΗ +); 3. · o-tolylamine formamidine 1,2,3,6-tetrahydronitrogen benzo [4,5Hepta-5, ethyl methanoate; MS (ES): 390 (ΜΗ +); 3- (1-methoxycarbonyl 2-methylpropylaminomethylammonyl), ι, 2,3,6_tetrahydronitrogen [4,5_b] 85585 -257- 200307684 ethyl indole-5-carboxylic acid; MS (ES) : 414 (MH +); 3- (6-Fluoro-4H-benzo [1,3] dioxolidine-8-ylaminomethylmethyl) -l, 2,3,6-tetrahydroazepine Benz [4,5Hepta] 4 丨 Ethyl indole-5-carboxylic acid; MS (ES): 452 (MH +); 3- (3,4-dihydro_2Hr · benzo [b] [l, 4] Dioxazepine-7-ylamine methylamidino) -1,2,3,6-tetrahydronitrile [4,5Hepta] Ethyl Acetate-5-Methyl Ester; MS (ES): 448 (MH +); 3- (4-bromophenylaminomethyl) -1,2,3,6- Hydrogen and nitrogen enzymatic [4,5_b] indole-5-carboxylic acid ethyl ester; MS (ES): 454 (MH +); 3- (1-fluorenyloxycarbonylhexahydropyridin-4-ylaminemethylmethyl) · 1,2,3,6-tetrahydronitrocarbazone [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES): 517 (MH +); 3- (2,4-dimethoxy Aniline (methylanilide) -1,2,3,6-tetrahydronitrocarba [4,5Hepta] doline · 5 · carboxylic acid ethyl ester; MS (ES): 436 (ΜΗ +); 3- ( 9H-fluoren-9-ylaminomethylmethyl) · 1,2,3,6-tetrahydronitrogeno [4,5-b] oxindole-5-carboxylic acid ethyl ester; MS (ES): 464 ( MH +); 3- (4-Chloro_2.methylanilinemethyl) -1,2,3,6-tetrahydronitrocarba [4,5Hepta] oxindole-5-carboxylic acid ethyl ester; MS (ES): 424 (ΜΗ +); 3- (4-bromo-3_methylanilinemethyl) -1,2,3,6-tetrahydronitrogeno [4,5hepta] oxindole Ethyl-5-carboxylic acid; MS (ES): 468 (MH +) · Example 74 3- (2 • Bromo-5-methoxybenzyl) -1,2,3,6-tetrahydroazepine Preparation of Benzene [4,5-8] Ethyl Ezanol-5, 5-Acrylate 85055 -258- 200307684

A. In a solution of 2-bromo-5-methoxybenzoic acid (240 µl, 0.25M in 1.0MDIEA in DMF), add a dmf (120 µm) using a robotic pipette. Liters, 0.5M solution, ~ 23 mg) HBTU and 1,2,3,6_tetrahydronitrogenated [4,5 hepta] indole-5-carboxylic acid ethyl ester (80 microliters, 0.25 M solution (~ 5 mg), 0.02 mmol). The mixture was shaken at 20 ° C overnight. The solvent was evaporated to obtain a crude product, which was redissolved in EtO Ac and purified by treatment with an aqueous solution. The solvent was evaporated, and the crude product was obtained, which was further purified by ion exchange (250 mg SCX). Next, the compound was further purified by HPLC-MS to obtain the compound (~ 2.75 mg, based on the ELSD calibration curve, the estimated weight); MS (ES): 469 (MH +); Β. The following compounds were used in this way Made from appropriately substituted carboxylic acids: 3- [2_ (4-pyridin-4-ylmethylhexahydropyridine) ethenyl] -1,2,3,6_tetrahydronitrogen [4 , 5-b] indole-5_carboxylic acid ethyl ester; MS (ES): 474 (ΜΗ +); 3_ [2- (4-naphthalen-1-ylmethylhexahydro 12-south-1-yl ) Acetyl] -1,2,3,6-tetrahydronitrogeno [4,5-b] W-Ethyl-5 side acid ethyl ester; MS (ES): 523 (MH +); 3- {2- [ 4- (2-Morpholin_4_yl_2_ketoethyl) hexahydropyridine_1_yl] acetamidine 1,2,3,6-tetrahydronitropyrene [4,5 Seven; j indole-5-carboxylic acid ethyl ester; MS (ES): 510 (MH +); 85585 -259- 200307684 3- [2- (4,4-dimethyl · 4,5-dihydroimidazole small (Ethyl) ethenyl] · 1,2,3,6_tetrahydronitrogeno [4,5-b; N indole-5-carboxylic acid ethyl ester; MS (ES): 395 (ΜΗ +); 3- {2- [4- (1-phenylethyl) hexahydropyhex-1-yl] ethenyl} -i, 2,3,6-tetrahydronitrogen [4,5-bH indole_5 _Ethyl carboxylate; MS (ES): 487 (MH +); 3- {2- [4- (2 · methoxyethyl) hexahydrobatch_ -1- ] Ethynyl} -i, 2,3,6-tetrahydronitrocarbazone [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES): 441 (MH +); 3 · [2 -(1,2-dimethyl-propylamino) -ethenyl] -1,2,3,6-tetrahydronitrogeno [4,5seven] ... ethyl indole-5-carboxylic acid; MS ( ES): 384 (MH +); φ 3- [2- (3-methylhexahydroρ biden-1-yl) ethynyl] -1,2,3,6-tetrahydronitrogen [4, 5VII] 4 丨 Ethyl indole-5-carboxylic acid; MS (ES) ·· 396 (ΜΗ +); 3- (2-Ethylaminoethylethyl) -1,2,3,6-tetrahydronitrogen Phyto [4,5-b] 4 丨 Homo-5-chinoic acid ethyl ester; MS (ES): 404 (MH +); 3- (2-hexahydropyridin-1-ylethylfluorenyl) -1,2 , 3,6-Tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES): 382 (MH +); 3- (2 · Mafulin-4 · ylethyl (Methenyl) -1,2,3,6_tetrahydronitrogeno [4,5-b] indoma-5-acrylic acid ethyl ester; MS (ES): 384 (MH +); # 3- (2- Methyl_3_trifluoromethylbenzoate) -1,2,3,6-tetrahydronitrocarba [4,5-b] K 丨 Homo_ 5-carboxylic acid ethyl ester; MS (ES): 443 (MH +); 3- [2- (2.Bromophenyl) ethenyl] 1,2,3,6_tetrahydronitrogeno [4,5Hepta] ardol-5_carboxylic acid ethyl ester; MS (ES): 453 (MH +); 3-Ethyl-1,2,3,6-tetrahydronitrocarba [4,5Hepta] indole-5-carboxylic acid ethyl ester; MS (ES): 299 (MH +); 3- (2,4-xylylenemethyl) -1,2,3,6-tetrahydronitrogen is benzo [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES): 389 (MH +); 85585 -260-200307684 3- (4-benzylbenzylhydrazyl) -i, 2,3,6-tetrahydronitrogeno [4,5-b] ^ indole- Ethyl 5-carboxylate; MS (ES): 451 (MH +); 3- (2,5-xylmethylmethyl) -i, 2,3,6-tetrahydronitrogen [4,5-b ] WNoise_5_carboxylic acid ethyl ester; MS (ES): 389 (MH +); 3- (5 • chloro-2-methylbenzyl) -1,2,3,6-tetrahydro nitrogen Homo [4,5Hepta] indole-5_carboxylic acid ethyl ester; MS (ES): 409 (MH +); 3- (2-bromo-4-methylbenzyl) -1,2, 3,6-tetrahydronitrile [4,5-b] W 丨 Homo-5-acid ethyl ester; MS (ES): 453 (MH +); 3 · [1- (4-chlorophenyl) _ Cyclopropanecarbonyl] -1,2,3,6 · tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid ethyl ester; MS (ES): 435 (MH +); 3- (benzo Furan-2-carbonyl) · 1,2,3,6-tetrahydronitrocarbazone [4,5Hepta] dodol-5_carboxylic acid ethyl ester; MS (ES): 401 (MH +); 3- [2 -(3,4 · dimethoxyphenyl) -acetoxy] -1,2,3,6-tetrahydronitrogeno [4,5_b], 5 丨 ethyl-5-carboxylic acid ethyl ester; MS ( ES) ·· 435 (MH +); 3- (4-p-tolylbutylfluorenyl) -l, 2,3,6-tetrahydronitrogen [[5,5_b] 4j] _5 _Ethyl Acetate; MS (ES): 417 (MH +); 3_ (2_Bromo_6_methylbenzoate) _1,2,3,6-tetrahydronitrogen is benzo [4,5-b ] W 丨 Homo-5-acrylic acid ethyl ester; MS (ES): 453 (MH +); 3- [3- (3-Bromophenyl) propenylmethyl] · 1,2,3,6-tetrahydronitrogen Ethyl [4,5 hepta] oxindole-5-carboxylic acid ethyl ester; MS (ES): 465 (ΜΗ +); 3- (2-bromo-5-methoxybenzyl) -1,2 , 3,6-Tetrahydronitrogeno [4,5 七] 啕 Acetyl-5-metanoate; MS (ES): 469 (ΜΗ +); 3 · (2,3-dichlorobenzyl) ) -1,2,3,6_tetrahydronitrogen benzo [4,5seven] indrum-5-metanoate ethyl ester; MS (ES): 429 (MH +); 85585 -261- 200307684 3- [2_ (4-Methoxyphenoxy) -ethenyl] -1,2,3,6-tetrahydronitrogeno [4,5-b] ^ indole-5-carboxylic acid ethyl ester; MS (ES ): 421 (MH +); 3- (3-Cyclo-5_trifluoromethylbenzylidenetetrahydronitrocarba [4,5Hepta] indole · 5-carboxylic acid ethyl ester; MS (ES) : 474 (MH +); 3- (2-Gas-3-methylbenzylidene) -1,2,3,6-tetrahydronitrocarba [4,5hepta] oxindole-5-carboxylic acid Ethyl ester; MS (ES): 409 (MH +); 3- (2-Bromo-3-methylbenzyl) -1,2,3,6-tetrahydronitrogen [4,5-15 ] Ethyl indole-5-carboxylic acid ethyl ester; MS (ES): 453 (MH +); φ 3- (3-methoxy-2-methylbenzyl) Radical) 1,2,3,6-tetrahydronitrogeno [4,5-b; ethyl indole-5-carboxylic acid; MS (ES): 405 (MH +); 3- (4-form Oxycarbonyl-3-nitrobenzyl)) 1,2,3,6-tetrahydronitrogeno [4,5-1 &gt;] pyrene-5-carboxylic acid ethyl ester; MS (ES): 464 (MH +); 3- (3-Chloro-2-methylbenzylidene) -1,2,3,6-tetrahydronitrogeno [4,5-bH 丨 indole-5-carboxylic acid ethyl ester ; MS (ES): 409 (MH +); 3- (2-p-tolyl-propionyl) -1,2,3,6-tetrahydronitrogen [4,5-b] pyridin-5 -Ethyl carboxylic acid; MS (ES): 403 (MH +); # 3- (4-Benzylamidinylbenzyl) -1,2,3,6-tetrahydronitrogen [4,5 七] Ethinyl-5-carboxylic acid ethyl ester; MS (ES): 465 (MH +); 3- (5-methoxy-2-nitrobenzyl) -1,2,3,6_tetrahydro Nitrogen [4,5_b] p5 丨 Hydroxy-5-carboxylic acid ethyl ester; MS (ES) ·· 436 (MH +); 3- (2 · &gt; Sulyl-5-methylbenzyl)- l, 2,3,6-tetrahydronitro τι and [4,5-b] p5 丨 Homo-5-acrylic acid ethyl ester; MS (ES): 453 (MH +); 3- (4-chloro- 2-methylbenzylidene) -1,2,3,6-tetrahydronitrocarba [4,5 七] 啕 -5--5-carboxylic acid ethyl ester; MS (ES) ·· 409 (MH +); And 85585 -262 · 200307684 3- (4 • Ethyl benzamidine) -l, 2,3,6-tetrahydrazine_nitrogen [4,5- bH 丨 Indole-5_carboxylic acid ethyl ester; MS (ES): 403 (MH +).

Example 7S Time-Resolved Fluorescence Resonance Energy Transfer (TR_FRET) Detection TR-FRET detection was performed in the following manner, using 8nMGST-farnesin X receptor-LBD (including glutathione-S-transferase) on the architecture Conjugated to the functional site of farnesin X receptor ligand binding (human farnesin X receptor amino acids 244-1471), 8nM 铕 labeled anti-GST antibody (Wallac / PE Life Science φ Cat AD0064), 16 ηΜ biotin-SRC-1 peptide [5'-Biotin-0P83ΙΚ8υΓΕΕΗΚΐυίΚΙχ () ΕΟ3Ρ1 €: 〇ΝΗ2], 20nMAPC-SA [Allophycocyanin conjugated streptomycin amino acid] (Wallac / PE Life Scientific Cat # AD0059A) in FRET detection buffer (20 mM KH2 P04 / K2 HP04 (pH 7.3), 150 mM NaCl, 2 mM CHAPS, 2mMEDTA, lmMDTT) in the presence of the test compound in a 384-well detection plate Incubate at room temperature for 2-4 hours. Data were collected using an LJL analyzer using standard operating instructions and conditions. The readings were obtained after a 65 microsecond delay at emission wavelengths of 615 nm and 665 nm, and excitation wavelengths of 330 # nm. Example 76 Co-transfection Detection A basic co-transfection proposal to measure the activity of farnesin X receptors is described below. CV-1 African green monkey kidney cells were covered 24 hours before metastatic infection to achieve approximately 70-80 percent confluence. Cell lines were transfected with the following expression vectors: CMX · farnesin X receptor (full-length human farnesin X receptor), CMX-RXR α (full-length human RXR), Lucl2 ((ECREx7-Tk-worm fluorescence) Enzyme) Luciferin 85585 • 263 • 200307684 Enzyme reporter gene construct (see WO 00/76523, Venkateswaran et al. (2000) J. Biol. Chem. 275 14700_14707). Use CMX-cold galactosidase The expression vector was used as a control group for metastatic infection. The metastatic infection agent used was DOTAP (Boehringer Mannheim). The cells were cultured for 5 hours with a DOTAP / DNA mixture, and then the cells were collected and covered to a well 96 containing an appropriate concentration of the test compound or 384-well plate. Allow the test to continue for another 18-20 hours, then lyse buffer (1% tritonX 100, 10% glycerol, 5 mM dithiothreitol, 1 mM EGTA, 25 mM lutein , PH 7.8) to lyse the cells and luciferase detection buffer (0.73 mM ATP, 22.3 mM flavonoids, (XllmMEGTA, 0.55mM luciferin, 0.15mM Coenzyme A, 0.5mMHEPES, 10mM magnesium sulfate) In the presence of a standard luminometer plate reader (PE Biosyst ems, NorthStar reader), using the recommended operating instructions and conditions to measure luciferase activity. Example 77 In vivo studies To assess that the main target gene is directly regulated by the compound of the invention, animals are administered to the test compound A single oral dose, and tissues were collected at six or fifteen hours after taking. Male C57BL / 6 mice (n = 8) were orally administered with vehicle or compound by oral gavage. Six and At fifteen hours, blood was collected from the animals through the posterior sinus node and collected for plasma. Then, the animals were euthanized, and tissues such as liver and intestinal mucosa were collected and frozen suddenly for further analysis. Analysis of plasma lipid parameters, such as Total cholesterol, HDL cholesterol, and triglyceride content. RNA can be extracted from frozen tissues, and the main target genes can be analyzed by quantitative real-time PCR. To confirm the specificity of the target gene regulation by the farnesin X receptor In this same proposal, the mouse (farnesin X receptor 1-) and the C57BL / 6 wild-type control group that have been eliminated by 85585 -264- 200307684 can be used. For comparison compounds Effects on plasma lipid morphology, including, but not limited to, cholesterol and triglycerides, allow animals to take compounds for a week, and monitor plasma lipid levels throughout the study. Male C57BL / 6 mice (n = 8) were borrowed daily Vehicle or compound is administered by oral gavage. Plasma samples were taken on days (to group animals) and taken on days 1, 3, and 7. Three hours after the dose was taken, samples were collected. On day 7 of this study, animals were euthanized after plasma collection, and tissues, such as the liver and intestinal mucosa, were left cold for further analysis. Analyze plasma lipid parameters such as total cholesterol, cholesterol, and triglyceride levels. RNA was extracted from frozen tissue for later analysis of the regulation of major target genes by quantitative real-time PCR. In order to confirm the specificity of the target gene regulation by the farnesin X receptor, the excluded mouse and the C57BL / 6 wild-type control group can be used in the same proposal. Assessment of the compounds' inhibition of cholesterol absorption is achieved through a measure of labeled cholesterol in the feces. Male A129 mice (n = 7) were orally administered with vehicle or compound daily for 7 days. On day 7 of the study, animals were administered [14 C] -cholesterol and [3h] -dihydrositosterol by oral gavage. The animals were individually housed on a metal mesh rack for the next 24 hours to collect feces. Then, the feces are dried and ground into a fine powder. The labeled cholesterol and dihydroglutanol were extracted from the feces and the ratio of the two was counted on a liquid scintillation counter to evaluate the amount of cholesterol absorbed by individual animals. The test of selected compounds disclosed in this article is to modulate the content of triglyceride and cholesterol in normal, hyperlipidemia, atherosclerotic and dyslipidemia and diabetes animal models 85585-265- 200307684. ability. Further reductions in lipids and glucose were also detected. For example, in normal mice, 3- (3,4-difluorobenzyl) _u_: methyl · 12 3, heart tetraqi · nitrogen exocytosis · acetate · 5 · acetic acid is aimed at mg / kg After taking the medicine once a week, the plasma triglyceride content was significantly reduced. At 10 mg / kg, the plasma total biliary system was reduced every week after taking the medicine, without affecting the plasma HDL · cholesterol content. The decrease in total plasma cholesterol can be attributed to the significant reduction in plasma non-HDL cholesterol in normal mice. In animal models of hyperlipidemia and atherosclerosis, such as low-density lipoprotein receptor-deficient mice (LDLR-/-) that consume Western-style diets (high-fat and cholesterol supplements), 3- (3,4 -Difluorobenzyl dimethyl 1,2,3,6 tetrahydro · nitro-p- [4,5-b] indole-5-carboxylic acid ethyl ester at 10 mg / kg daily At the end of the week of taking the drug, the plasma triglyceride was significantly reduced by more than 50%. The total plasma cholesterol content was also reduced by ~ 50% in response to this medication use method, accompanied by the reduction of non-HDL cholesterol. In addition, the plasma was free Fatty acid and glucose concentration are also due to 3- (3,4-difluorobenzyl dimethyl sulfonium 2,3,6_four winds and [4,5-b] 4 丨 Homo-5-carboxylic acid Diluted with ethyl ester treatment. In animal models of diabetes and dyslipidemia, such as db / db mice, the plasma lipid profile is similarly caused by 3- (3,4_difluorobenzyl) once a day. ) 1,1_dimethyl-1,2,3,6-tetrahydro · azepine [4,5-b] indole-5 · carboxylic acid ethyl ester, treated at 10 mg / kg for one week and Improved, causing individual plasma triglycerides and non-HDL cholesterol Decrease by about 50%. In this mode, a decline in plasma free-state fatty acid content was also detected. Results of Examples 75 and 76 85585 -266- 200307684 Co-transfection of fenfarin X receptor / ECREx7 (Example 76 ) And TR-FRET test (Example 75) can be used to establish the EC50 / IC5 () value to provide medicinal effects, as well as the efficacy or percent inhibition. The efficacy is defined as the compound relative to the control group (goose go Oxycholic acid, CDCA) or low control group (DMSO / vehicle) &lt; activity. The dose response curve was generated from a I8 point curve with a concentration difference of 1/2 log unit. Each point represents the data obtained from 384 well plate data. The average of 4 wells. The curve of the data is generated using the following equation: Y = bottom shao + (top-bottom) / (l + 10A ((LogEC50_X) * slope slope)) So the 'EC50 / ICs〇 system is defined The concentration at which the half-high value response between the top (maximum) and bottom (baseline) values of the activator or antagonist is elicited. The indicated EQo / ICw value is the average of at least 3 independent experiments. The relative efficacy of the activator Or control group%, measured by The maximum response is compared 'The maximum response is measured individually in each dose response experiment. For antagonist detection, CDCA was added to each well of a 384-well plate to elicit a response. Therefore, the% inhibition of each antagonist , Is a measure of CDCA activity inhibition. In this example, 100% inhibition means that the activity of CDCA has been reduced to the baseline content, and the baseline content is defined as the detection activity only in the presence of DMS. Most of the compounds disclosed and tested in the test showed activity in at least one of the above tests (EC5G or IC5G below 10 / zM). Most showed activity below 1 / zM. For example, the following examples of compounds, when measured by a co-transfection assay, all show activator activity with less than 1 EC50 and greater than 100% efficacy: 85585 • 267- 200307684 3 (4-fluorobenzyl) ) -2-methyl-1,2,3,6_tetrahydroazepine [4,5 hepta] indole-5-carboxylic acid n-propanthine; 3- (3-fluorobenzyl) -1,2,3,6-tetrahydronitropyrene [4,5Hepta], 5 丨 indole-5-carboxylic acid ethyl ester; 3- (4-fluorobenzylidene) -1,2,3, 6-tetrahydronitropyrene [4,5Hepta] pyridine-5-carboxylic acid cyclobutylamidine; and 3- (4-fluorobenzyl) -2-methyl-8-fluoro-1 , 2,3,6-tetrahydronitrogen is benzo [4,5-bH 丨 indole-5-propanoic acid n-propyl ester. The compounds exemplified below, when measured by one or more in vitro assays described herein, show activator activity, have less than 100 nMEC5G, and greater than 100% efficacy: 3- (3,4-difluorobenzyl Fluorenyl) small methyl-tetrahydronitrogeno [4,5 hepta] indole-5-carboxylic acid ethyl ester; 3- (3,4-difluorobenzylfluorenyl) -l, l-dimethyl _ι, 2,3,6-tetrahydronitrile calls for [4,5-b] indh-5-acetylacetate; 3- (4_fluorobenzyl) -2-methyl-1,2 , 3,6-tetrahydroazepine [4,5Hepta] pyridine-5-carboxylic acid cyclobutylamidamine; 3 · (3,4 · difluorobenzyl) 4,1 · dimethyl _i, 2,3,6-tetrahydrazine is benzo [4,5-b] indone-5_isopropyl isopropionate; and 3- (3,4-difluorobenzyl) small methyl group Tetrahydronitrogen is isopropyl [4,5-b] indole-5-carboxylic acid. The compounds exemplified below show antagonist activity when measured by one or more of the in vitro assays described herein, with IC5G below 100 nM and 100% inhibition. 8- (3 · cyclopropyl-1- Methylureido) _3_ (4 · fluorobenzylidene) -1,1 · dimethyl-1,2,3,6 · 85585 -268 · 200307684 tetrahydronitrogen [4,5 七] 4 丨I ethyl ethyl acid; 3- (4-fluorobenzyl) -U-dimethyl-8- (1-methyl · 3-pyridin-2-ylmethylureido) _1,2, 3,6-tetrahydronitrogenates [4,5 七] 啕 11 ethyl-5--5-acrylic acid ethyl ester; 3- (4-fluorobenzyl) -U-dimethylisopropylamine formamidine Ethyloxy-1,2,3,6-tetrahydronitrogeno [4,5Hepta] 4 丨 Ethyl Acetate; 8-Cyclopropylaminemethylamidooxy-3- (4-fluorobenzene (Methylamidino) _!,; [_Dimethyl-1,2,3,6-tetrahydronitropyro [4,5-bH 丨 indole-5-carboxylic acid ethyl ester; and 3- (4-fluoro Benzamidine) -1,1-dimethyl-8-phenphen-2-ylmethylamine methylaminooxy) -1,2,3,6-tetrahydronitrogeno [4,5 七] Indole-5_carboxylic acid ethyl ester; The compounds exemplified below, when measured by one or more of the in vitro assays described herein, all show some activators, with EC5G and IC5. Less than 200 πM with 10-30% efficacy and 70-90% inhibition: 8-cyclohexylamine formamyloxy_3- (4-fluorobenzyl) -amidine, amidine-dimethyl-1, 2,3,6-Tetrahydronitrogeno [4,5-b] Windole-5_carboxylic acid ethyl ester; 3- (4-fluorobenzylidene) -1,1_dimethyl_8- (5-Methylpyridin-2-ylmethylaminomethylamidoxy) 1,2,3,6_tetrahydronitrocarba [4,5-b] indole · 5-acrylic acid ethyl ester; 3- (4-fluorobenzylidene) -1,1-dimethyl each (2 • pyridin-2-yl-ethylaminomethylamidooxy M, 2,3,6-tetrahydronitro [4,5-b] Indole-5-carboxylic acid ethyl ester; 3- (4-fluorobenzylidene) -1,1-dimethyl each (pyridine · 2-yl-methylamine formamyloxy) H, 2,3,6, hydrogen, nitrogen, [4,5-bH indole-5-carboxylic acid ethyl ester; and 3 &lt; 4-fluorobenzyl dimethyl-8_ (pyridyl | ylmethylamine Formamyloxy) _1,2,3,6_tetrahydronitrogen is fused with [4,5 heptamidine i carboxylic acid ethyl ester. Since the modification will be apparent to those skilled in the art, the present invention is only intended to Limited to the scope of the patent application park attached to the article. 85585 -269-

Claims (1)

200307684 Patent application park: ι · A compound of formula (I) or formula (π): Or a pharmaceutically acceptable derivative thereof, wherein η is 0 to 4; A is -N (R9)-, -0-, or -S (0) t- (wherein t is 0 to 2); R1 is Optionally substituted alkyl, optionally substituted alkyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, Optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, -OR14, -N (R15) R16, -N (R17) N (R15) R16,- C (0) R18, -C ^ OR14 &gt; -C (S) 0R14--C (0) SR14--C ^ NCR15) RX 6 '-C (0) N = NR16 or -CXCOl ^ R17) N ( Ri 5) Ri 6; R 2 is hydrogen or optionally substituted alkyl; or R 1 and R 2 and the atoms to which they are attached together to form a optionally substituted cycloalkyl, optionally substituted heterocyclyl, Optionally substituted aryl or optionally substituted heteroaryl ring; 85585 200307684 R3 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally Substituted cycloalkyl, optionally substituted aryl, optionally Aralkyl, bismuth-substituted heteroaryl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, -C (0) R10, -C (0) 0R1 (),- S (0) 2R1 (), 〇〇〇) Ν (Κη) Κ10 ^ -C (0) N (R11) N (R12) RX 0 '^ (R11) C (0) R10'-N (R! 1) C (0) N (R12) R! 0 &gt; -N (Ru) C (0) N (R12) N (R13) R10-^ (R11) 0 (0) 0 ^ 0 '-P (0 ) 〇R10 or -p (o) (or19) or1 (); Reference R4 is hydrogen, optionally substituted alkyl, optionally substituted feminine, optionally substituted alkynyl, optionally substituted Aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl,- C (0) R18, -C (0) OR2 (), -C (0) N (R21) R22 or -C (0) N (R42) N (R21) R22; R5, R6 and R7 are each independently hydrogen , Optionally substituted alkyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, -OR14,-φ S (0) 2R14, -N (R15) R16, -C (〇 ) R18, -C (0) OR2〇 or -C (0) N (Rn) R22; or R4 and R7, or R4 and R5, or 圮 and! ^, Or ^ and! ^, Or ^ and] ^, or R6 and R7 'together form optionally substituted cycloalkyl, optionally substituted heterocyclyl, or optionally substituted cycloalkenyl ring; and other R4, R5, R6 And R7 are as described above; or R4 and R5 together form a keto group; and R6 and R7 are as described above; or R6 and R7 together form a keto group; and R4 and R5 are as described above; 85585 -2- 200307684 Selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, Halo, cyano, nitro, -C (0) OR23, -C (0) N (R24) R25, _C (〇) R26, -〇R2 7, -SR2 7 and -N (R28) R29, or Two R8 groups together form optionally substituted heterocyclyl or heteroaryl; R9 is hydrogen, optionally substituted alkyl or -S (〇) 2R43; RiO, R11, R12, R13 and R19 are Choose from ⑻ or (b) as follows: ⑻R11, R12, R13, and R19 are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, and optionally Substituted naphthenes , Optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; and R1G is deemed Optionally substituted alkyl, optionally substituted amidino, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally Optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; or (b) R1 G and R11, and / or R1G and R12, and / or R1G and R13, And / or R1G and R19, and / or R11 and R12, and / or R12 and R13, together with the atoms to which they are attached, form optionally substituted heterocycles or optionally substituted heteroaryl rings; and others R10, R11, R12, R13 and R19 are selected as in (a) above; R14, R15, R16 and R17 are selected as in ⑻ or (b): ⑻R14, R15, R16 and R17 are each independently hydrogen, Optionally substituted alkyl, optionally 200307684 substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl , Optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclic, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; or (b ) R15 and R16 together with the nitrogen atom to which they are attached together form a heterocyclic ring optionally substituted or a heteroaryl ring optionally substituted, and R14 and R17 are selected as above in ⑻. Optionally substituted alkyl, optionally substituted amidino, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally Case substituted heterocyclyl, optionally substituted heteroaryl or optionally substituted heteroaralkyl; R20, R21, R22 and R42 are selected from ⑻ or (b) as follows: ⑻R20, R21 , R22 and R42 are each independently hydrogen, optionally substituted alkynyl, optionally substituted amidino, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, Optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted Aryl or optionally substituted heteroaralkyl; or (b) R21 and R22 and the nitrogen atom to which they are attached together to form a optionally substituted heterocyclyl ring or optionally substituted heteroaryl ring R2G and R42 are selected in the above ⑻; R23, R24, R25, and R26 are selected in the following ⑻ or ⑼: ⑻] ^ 23, R24, R25, and R26 are each independently hydrogen, depending on the situation. Substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aryl 85585 -4- 200307684 alkane Base, optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; or (b) R24 and R25 and the nitrogen atom to which they are attached together to form a In the case of a substituted heterocyclic group or in the case of a substituted heteroaryl ring ', r2 3 and R2 6 are selected as ⑻ above; R27, R28 and R29 are selected as 下述 or (b) below : ⑻R27, r28 and R29 are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally Substituted alkynyl, optionally substituted aryl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, _C (〇) R3 G, -C (0) 0R3 1 or -C (0) N (R3 2) 圮 3 · •, or (b) R28 and R29 and the nitrogen atom to which they are connected together to form a substituted heterocyclic group or a case as appropriate A substituted heteroaryl ring, and R27 is selected from ⑻ above; R30 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted decyl, optionally Substituted cycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted _ heteroaryl Burning group; R31 is optionally substituted alkyl, optionally substituted dilute group, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted Aromatic aryl, optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; R32 and R33 Choose from the following ⑻ or ·: ⑻ Yi 32 and Hua 33 are each independently hydrogen, optionally substituted thiol, optionally substituted fluorenyl group 85585 200307684, optionally substituted block group, as appropriate Substituted hydrazone, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted hetero Aralkyl; or (b) R32 and R33 and the nitrogen atom to which they are attached together form optionally substituted heterocyclic ring or optionally substituted heteroaryl ring; R43 is optionally substituted alkyl , Optionally substituted fluorenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclic ring Base, optionally substituted heteroaryl group or optionally substituted heteroaryl group; each R ^ R33, R42 and R43, when substituted, is substituted by one or more substituents each independently selected from Q1 ; Q1 is radical, pseudo radical, hydroxyl, keto, thio, nitrile, nitro, formazan , Mercapto, hydroxycarbonyl, hydroxycarbonylalkyl, alkyl, alkyl, polyhaloalkyl, aminoalkyl, diaminoalkyl, alkenyl containing 1 to 2 double bonds, containing 1 to 2 Participating alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, heteroaryl, aralkyl, arylalkenyl, arylalkynyl, heteroaralkyl, Trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, alkylene, arylalkylene, alkylcarbonyl, cycloalkylcarbonyl, heterocyclylcarbonyl, Arylcarbonyl, heteroarylcarbonyl, oxycarbonyl, alkoxycarbonylalkyl, aryloxycarbonyl, aryloxycarbonylalkyl, aralkyloxycarbonyl, aralkyloxycarbonylalkyl, arylcarbonylalkyl , Aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl, diarylaminocarbonyl, aralkylaminocarbonyl, 200307684 alkoxyaryloxy, heteroaryloxy, hetero Aryloxy, heterocyclyloxy, cyclohexyloxy, perfluoroalkoxy, fluorenyloxy, alkynyloxy, aralkyloxy, tigercarbonyloxy, arylcarbonyloxy, aralkyl Carbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, aralkyloxycarbonyloxy, aminocarbonyloxy, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylaryl Aminoaminocarbonyloxy, diarylaminocarbonyloxy, guanidine, isothioureido, methylamido, alkylmethylamido, arylmethylamido, aminothiocarbonyl, alkylaminothiocarbonyl, Arylaminothiocarbonyl, amine, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, arylaminoalkyl, diarylaminoalkyl, alkylarylaminoalkyl , Alkylamino, dialkylamino, amidoamino, arylamino, diarylamino, alkylarylamino, alkylcarbonylamino, alkoxycarbonylamino, aralkyloxycarbonylamine Aryl, arylcarbonylamino, arylcarbonylaminoalkyl, aryloxycarbonylaminoalkyl, aryloxyarylcarbonylamino, aryloxycarbonylamino, alkylsulfonylamino, aryl Sulfosulfonylamino, heteroarylsulfonylamino, heterocyclylsulfonamido, heteroarylthio, azide, diazenyl, -N + (R34) (R35) R36, -P (R37) 2, -p (o) (r37) 2, -op (o ) (r37) 2, -n (r38) c (0) r39, dialkylphosphonic acid group, alkylarylphosphonic acid group, diarylphosphonic acid group, hydroxyphosphonic acid group, alkylthio group, aryl group Thio, perfluoroalkylthio, hydroxycarbonylalkylthio, thiocyano, isothiocyano, alkylsulfinamidooxy, alkylsulfamophenoxy, arylsulfinamidooxy, Arylsulfonyloxy'hydroxysulfonyloxy, alkoxysulfonyloxy, aminesulfonyloxy, alkylaminosulfonyloxy, dialkylaminosulfonyloxy, arylaminosulfonyl Fluorenyloxy, diarylaminosulfonyloxy, alkylarylaminosulfonyloxy, sulfonylsulfonyl, alkylsulfinylfluorenyl, alkanes 85585 -7- 200307684 sulfonylsulfonyl, aryl Sulfonylidene, alkoxysulfonyl, aminesulfonyl sulfonyl, arylamino sulfonyl, diaminosulfonyl sulfonyl; or square radicals Aminosulfonyl, dialkylaminoarylaminosulfonyl, or alkylaryl groups are Q1 groups, and their substitutions are u, and the 1 ~ heart atom system is arranged in the order of 2 or 1, 3 Together, forming a sulfenyl group, a lactosyl group, and a @s 入 k — liceyl, thioalkyloxy, or Alkyl dithiooxy; or Two Q1 base rings, which are substituted with the same atom,-form a secondary alkyl group; each of R4, R "and R36 is independently hydrogen, alkyl, aryl, aryl, heteroaryl, heteroaryl , Heterocyclyl or heterocyclyl alkyl; R37 is hydroxyl, alkoxy, aralkoxy, alkyl, heteroaryl, heterocyclyl, aryl or -NR4GR41; R40 and R41 are each independently hydrogen or alkane Radical, aralkyl, aryl, heteroaryl, heteroaralkyl or heterocyclyl, or R40 and R41 work together to form an alkylene, nitroalkylene, oxyalkylene, or thioalkylene group; R38 is hydrogen, alkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclic Or heterocyclylalkyl; and R39 is alkoxy, aralkoxy, alkyl, heteroaryl, heterocyclyl, aryl, or -N (R4 ();) R4i; each Q1 is independently Substituted, or substituted by one or more substituents each independently selected from Q2; each Q2 is independently halo, pseudohalo, hydroxy, fluorenyl, thio, nitrile, nitro, formamyl, mercapto, Hydroxycarbonyl, hydroxycarbonylalkyl, alkyl, 85585 200307684 haloalkyl, polyhaloalkyl, aminoalkyl, diaminoalkyl, fluorenyl group containing 1 to 2 double bonds, containing 1 to 2 parameters Bonded alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, heteroaryl, aralkyl, arylalkenyl, arylalkynyl, heteroaralkyl, triaryl Alkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, alkylene, arylalkylene, alkylcarbonyl, cycloalkylcarbonyl, heterocyclylcarbonyl, aromatic Carbonyl, heteroarylcarbonyl Alkoxycarbonyl, alkoxycarbonylalkyl, aryloxycarbonyl, aryloxycarbonylalkyl, aralkyloxycarbonyl, aralkoxycarbonylalkyl, arylcarbonylalkyl, aminocarbonyl, alkylaminocarbonyl , Dialkylaminocarbonyl, arylaminocarbonyl, diarylaminocarbonyl, aralkylaminocarbonyl, alkoxyaryloxy, heteroaryloxy, heteroarylalkoxy, heterocyclyloxy , Cycloalkoxy, perfluoroalkoxy, alkenyloxy, alkynyloxy, aralkoxy, alkcarbonyloxy, arylcarbonyloxy, aralkylcarbonyloxy, alkoxycarbonyloxy, aryl Oxycarbonyloxy, aralkyloxycarbonyloxy, aminecarbonyloxy, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylarylaminocarbonyloxy, diarylamino Carbonyloxy, guanidine, isothioureido, methylamido, alkylmethylamido, arylmethylamido, aminothiocarbonyl, alkylaminothiocarbonyl, arylaminothiocarbonyl, amino, aminoalkyl Alkyl, alkylaminoalkyl, dialkylaminoalkyl, arylaminoalkyl, diarylaminoalkyl, alkylarylaminoalkyl, alkylamino, dialkylamino, haloalkyl amine Group, arylamino group, diarylamino group, alkylarylamino group, alkylcarbonylamino group, alkoxycarbonylamino group, aralkyloxycarbonylamino group, arylcarbonylamino group, arylcarbonylamino group Group, aryloxycarbonylaminoalkyl, aryloxyarylcarbonylamino, aryloxycarbonylamino, alkylsulfonylamino, 85585 -9- 200307684 aryl ~ acidamino, heteroaryl Basic amino, heterocyclyl amino, heteroarylthio, azido, diazonium, -n + (r34) (r35) r36, -P (R) 2 P (〇) (R37) 2, -〇P (0) (R37) 2, -N (R38) C (0) R39, dialkylphosphonic acid sulfonyl squaranoic acid group, diaryl pentanoic acid group, meridian group Titanic acid, fluorenyl, square thio, perfluoroalkylthio, hydroxycarbonylalkylthio, cyano, cyano, alkylsulfinyloxy, alkylsulfonyloxy , Arylsulfinyloxy arylsulfonyloxy, hydroxysulfonyloxy, fluorenyl ~ fluorenyloxy, aminosulfonyloxy, alkylaminosulfonyloxy, dialkylamine Continued alkoxy, arylamine continued oxy, diarylamine Glycan, succinyl, succinyl, succinyl, aryl, succinyl, succinyl Alkyl, diamine amino% fluorenyl, arylaminosulfonyl, diarylaminosulfonyl or alkylarylaminosulfonyl; or, two Q groups, substituted atom systems In the form of 丨, 2 or i, 3, and together form a secondary group, an oxygen secondary group, a secondary group dioxy group, a thio group secondary group, or a secondary alkyl group dithiooxy group; or two Q2 groups, It is substituted with the same atom to form an alkylene group, with the proviso that if R8 is hydrogen or _〇CH3, then R3 is not hydrogen, methyl, ethyl, -CH2C6H5, -CH (CH3) C6H5, CH ( CH3) fluorenyl or &lt;: (〇) (χ: 2Η5), with the proviso that if R3 is hydrogen, then R8 is not hydrogen, nitro, lower alkoxy, self-radical, or hydroxyl. 2. The compound according to item 1 of the scope of patent application, wherein the compound is a compound of formula (Ia) 85585 -10-200307684: Or a pharmaceutically acceptable derivative thereof, wherein: η is 0 to 4; A is _N (R9)-, -〇-, or -S (0) t · (wherein t is 0 to 2); φ R1 is Optionally substituted alkyl, optionally substituted amidino, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, Optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, -0, 14, collar 1115) 1116,-] ^ (1117) wind 1115) 1116, &lt; (0) 1 ^ 8, C (0) 0R14 ^ -C (S) OR14 '-C (0) SR14--C ^ NCR15) R2 6' -C (0) N = NR16 or 7 ^ (R15 )! ^ 6; R2 is hydrogen or optionally substituted alkyl ·, or ® R1 and R2 and the atom to which they are connected together to form a substituted cycloalkyl group and a substituted heterocyclic ring as appropriate Base, optionally substituted aryl or optionally substituted heteroaryl ring; R3 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally Substituted cycloalkyl, optionally substituted aryl, optionally substituted aryl Base, optionally substituted heteroaryl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, -C (0) R10, -C (0) OR10, -s (0) 2Rl0 , (⑼ 专 11 '85585 -11- 200307684,-¢: (0) 1 ^ (1111) N (Ι ^ 2 ID10, -NXR11) (:( 0) 1110, -NCR11) (:( 0) ^ 1112 Sense 10-^ (R11) 0 (0) ^^ 2 3 0 '-NCR11) 0 (0) 0 ^ 0' -P (〇) OR10 or _p (o) (or19) or10: R4 is hydrogen, Optionally substituted alkyl, optionally substituted amidino, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, Optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, -C (0) R18, -C (0) OR2〇, _C (0) N (R21 ) R22 or-· C (0) N (R42) N (R21) R22; R5, R6 and R7 are each independently hydrogen, optionally substituted alkyl, optionally substituted aralkyl, optionally substituted Heteroaralkyl, -01114, -S (0) 2R14, -N (R15) R16, -C (0) R18, -C (0) 0R2. Or -C (0) N (R21) R22: or R4 and R7, or R4 and R5, or R4 and R6, or R5 and R7, or R5 and R6 'or R6 R7 together to form optionally substituted cycloalkyl, optionally substituted heterocyclyl or optionally substituted cycloalkenyl rings; and other R4 #, R5, R6 and R7 are as described above; or R4 and R5 — Form keto groups; and R6 and R7 are as described above; or R6 and R7 together form keto groups, and R4 and R5 are as described above; each R8 is independently selected from hydrogen, optionally substituted alkyl, and Case substituted alkenyl, optionally substituted block, optionally substituted aryl, optionally substituted heteroaryl, halo, pseudo-fluorenyl, cyano, nitro, -C (〇) 〇R23, -C (0) N (R24) R25, -C (0) R26, -OR2 7, -SR2 7 and -N (R28) R29; 85585 -12- 200307684 R9 is hydrogen. Alkyl or -S (〇) 2R43; R10, R11, R13, and R19 are selected from the following ⑻ or (b): ⑻R11, R12, R13, and R19 are each independently nitrogen, as appropriate Substituted alkyl, optionally substituted alkenyl, optionally substituted block, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted Substituted heterocycle Base, optionally substituted heteroaryl, or optionally substituted heteroaryl, and R1 G is optionally substituted tiger, optionally substituted fluorenyl, and optionally substituted decyl _, Optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaryl Aralkyl; or 101110 and Rl1, and / or R10 and R12, and / or R1G and Rl3, and / or RlG and Rl9, and / or R11 and R1 2, and / or R12 and R13, and to which they are connected Atoms, together form optionally substituted heterocyclic rings or optionally substituted heteroaryl rings; and other R10, R11, R12, R13 and R19 are selected as above ⑻; R14, R15, feet 16 And the ruler 17 is selected from ⑻ or ⑼: ⑻R14, r15, R16, and R17 are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted block, or Optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted Heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; or (b) R15 and R16 and the nitrogen atom to which they are attached together to form a optionally substituted heterocyclyl ring Or optionally substituted heteroaryl rings, and R14 and R17 are selected as above, 85585 -13- 200307684 R18 is optionally substituted alkyl, optionally substituted fluorenyl, and optionally Substituted block group, optionally substituted cycloalkyl group, optionally substituted aryl group, optionally substituted aryl tiger group, optionally substituted heterocyclic group, optionally substituted heteroaryl group or optionally In the case of substituted heteroaralkyl; R20, R21, R22 and R42 are selected from ⑻ or (b) below. ⑻ R20, R21, R22 and R42 are each independently hydrogen, optionally substituted alkyl, Optionally substituted fluorenyl, optionally substituted block, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl , Optionally substituted heteroaryl or optionally substituted heteroaralkyl; or (b) R21 R22 and the nitrogen atom to which they are connected together form a heterocyclic ring optionally substituted or a heteroaryl ring optionally substituted, and R2G and R42 are selected as above; R23, R24, R25 And R26 are selected from ⑻ or (b) as follows: ⑻R23, R2 4, R2 5 and R2 6 are each independently hydrogen, optionally substituted alkynyl, optionally substituted alkenyl, optionally substituted Decyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heteroaryl or optionally A substituted heteroaralkyl group; or (b) R24 and R25 and the nitrogen atom to which they are attached together to form a heterocyclic group optionally substituted or a heteroaryl ring optionally substituted, and R23 and R26 is selected from ⑻ as above; r27, r28 & R29 is selected from ⑻ or 下述 as follows: ⑻R27, R28, and R29 are each independently hydrogen, optionally substituted alkyl, and optionally substituted 85585- 14 · 200307684 alkenyl, optionally substituted alkynyl, optionally substituted aryl, as appropriate Substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, -C (〇) r3 〇, -C (0) OR3 1 or -C (〇) N (R3 2) R3 3; or halogenated 28 and R29 and the nitrogen atom to which they are attached together to form a heterocyclic ring optionally substituted or a heteroaryl ring optionally substituted, and r27 is in ⑻ as above Choice; R30 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally Optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; R3 1 is optionally substituted alkyl, optionally Substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aromatic alkyl, optionally substituted heterocyclyl, optionally Case substituted heteroaryl or optionally substituted heteroaralkyl; ^ R3 2 and R3 3 are selected from ⑻ or (b) as follows: ⑻R3 2 and R3 3 Each independently is hydrogen, optionally substituted tiger, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkynyl, optionally substituted aryl, optionally substituted Substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; or (b) R32 and R33 and the nitrogen atom to which they are attached ' Together to form a substituted heterocyclic group or a substituted heteroaryl group depending on the condition of the stomach? R43 is an optionally substituted alkyl group, an optionally substituted alkenyl group, as indicated by 85585 .15- 200307684 Substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterofluorenyl, optionally substituted heteroaryl, or Optionally substituted heteroaralkyl; ^ Ri-R33, R42 and R43, when substituted, are substituted with one or more substituents each independently selected from Q1; Q1 is halo, pseudohalo, hydroxy , Keto, thio, nitrile, nitro, methyl, methyl, carbonyl, carbonyl, carbonyl _Alkyl, polyhaloalkyl, aminoalkyl, diaminoalkyl, alkenyl containing 1 to 2 double bonds, alkynyl containing 1 to 2 reference bonds, cycloalkyl, cycloalkylalkane Base, heterocyclyl, heterocyclylalkyl, aryl, heteroaryl, aralkyl, arylalkenyl, aryl block: aryl, heteroaryl, trialkyl, trialkyl, dialkyl Alkyl, alkyldiarylsilyl, triarylsilyl, alkylene, arylalkylene, alkylcarbonyl, cycloalkylcarbonyl, heterocyclylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkoxy Carbonyl, alkoxycarbonylalkyl, aryloxycarbonyl, aryloxycarbonylalkyl, aralkyloxycarbonyl, aralkoxycarbonylalkyl, arylcarbonylalkyl, aminocarbonyl, alkylaminocarbonyl, Alkylaminocarbonyl, arylaminocarbonyl, diarylaminocarbonyl, aralkylaminocarbonyl, aryloxyaryl, heteroaryloxy, heteroaryloxy, heterocyclyloxy, ring Alkoxy, perfluoroalkoxy, fluorenyloxy, alkynyloxy, aralkyloxy, alkoxycarbonyl, arylcarbonyloxy, aralkylcarbonyloxy, alkoxycarbonyloxy, aryloxy Carbonyloxy, Alkoxycarbonyloxy, aminocarbonyloxy, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylarylaminocarbonyloxy, diarylaminocarbonyloxy, guanidine, isopropyl Thiourea 85585 • 16-200307684 group, methylformyl, alkylformyl, arylformyl, aminothiocarbonyl, alkylaminothiocarbonyl, arylaminothiocarbonyl, amine, aminoalkyl, Alkylaminoalkyl, dialkylaminoalkyl, arylaminoalkyl, diarylaminoalkyl, alkylarylaminoalkyl, alkylamino, dialkylamino, alkylamino , Arylamino, diarylamino, alkylarylamino, alkylcarbonylamino, alkoxycarbonylamino, aralkyloxycarbonylamino, arylcarbonylamino, arylcarbonylaminoalkyl , Aryloxycarbonylaminoalkyl, aryloxyarylcarbonylamino, aryloxycarbonylamino, alkylsulfonylamino, arylsulfonylamino, heteroarylsulfonylamine Group, heterocyclylsulfonylamino, heteroarylthio, azide, diazenyl, N + (Κ34) (Κ35) Ϊ136, -P (R37) 2, -p (o) ( r37) 2, -op (o) (r37) 2, -N (R38) C (0) R39, dioxane Phosphonic acid group, alkylarylphosphonic acid group, diarylphosphonic acid group, hydroxyphosphonic acid group, alkylthio group, arylthio group, perfluoroalkylthio group, sulfanylthio group, thiocyano group , Isothiocyano, alkylsulfinyloxy, alkylsulfinyloxy, arylsulfinyloxy, arylsulfinyloxy, hydroxysulfinyloxy, alkoxysulfinyl Oxy, amine sulfonyloxy, alkylamino sulfonyloxy, dialkylamine® carbaryl, arylaminocontinuous oxy, diarylamine sulfonyloxy, alkylaryl Aminosulfonyloxy, sulfonylsulfenyl, alkylsulfinylsulfonyl, alkylcontinuous, arylsulfinyl, arylsulfinyl, mesinylsulfinyl, alkoxysulfinyl , Aminosulfonyl, alkylaminosulfonyl, dialkylamino continuous, diarylamine, diarylamino, or tigerylarylaminosulfonyl; or two Q1 groups in which the substituted atom system is arranged in 1,2 or 1,3, and together form an alkylene group, an oxyalkylene group, an alkylenedioxy group, a thioalkyloxy group, or an alkylene group 85585 -17- 200307684 Dithiol; or two Q1 groups' which are identically substituted R34, R35 and R36 are each independently hydrogen, alkyl, aryl, aralkylheteroaryl, heteroaralkyl, heterocyclyl or heterocyclylalkyl; R37 is hydroxy, Carbooxy, aralkoxy, alkyl, heteroaryl, heterocyclyl, aryl or -NR4GR41; R40 and R41 are each independently hydrogen, alkyl, aralkyl, aryl, heteroaryl, heteroaryl Alkyl or heterocyclic group, or R40 and R41 together form an alkylidene, nitroalkylene, oxyalkylene, or thioalkylene group; R38 is hydrogen, alkyl, aryl, aralkyl, heteroaryl , Heteroarylalkyl, heterocyclyl, or heterocyclylalkyl; and R39 is alkoxy, aralkyloxy, alkyl, heteroaryl, heterocyclyl, aryl, or -N (R4 ()) R41; Each Q1 is independently unsubstituted or converted by one or more substituents each independently selected from Q2; ® Each Q2 is independently halo, pseudohalo, hydroxyl, keto, thio, nitrile, Nitro, formamyl, mercapto, hydroxycarbonyl, hydroxycarbonylalkyl, alkyl, haloalkyl, dodecyl, aminoalkyl, diaminoalkyl, alkenyl containing 1 to 2 double bonds Alkynyl, naphthenes containing 1 to 2 references , Cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, heteroaryl, aralkyl, arkenyl, aralkynyl, heteroaralkyl, trialkylsilyl, dialkyl Arylsilyl, alkyldiarylsilyl, triarylsilyl, alkylene, arylalkylene, alkylcarbonyl, cycloalkylcarbonyl, heterocyclylcarbonyl, 85585 -18- 200307684 arylcarbonyl, Heteroarylcarbonyl, alkoxycarbonyl, alkoxycarbonylalkyl, aryloxycarbonyl, aryloxycarbonylalkyl, aralkoxycarbonyl, aralkyloxycarbonylalkyl, arylcarbonylalkyl, aminocarbonyl , Alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl, diarylaminocarbonyl, aralkylaminocarbonyl, alkoxyaryloxy, heteroaryloxy, heteroarylalkoxy, Heterocyclyloxy, cycloalkoxy, perfluoroalkoxy, alkenyloxy, alkynyloxy, aralkyloxy, alkcarbonyloxy, arylcarbonyloxy, aralkylcarbonyloxy, alkoxy Carbonyloxy, aryloxycarbonyloxy, aralkyloxycarbonyloxy, aminecarbonyloxy, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylaryl Aminocarbonyloxy, diarylaminocarbonyloxy, guanidine, isothioureido, formamyl, alkylformamyl, arylformamyl, aminothiocarbonyl, alkylaminothiocarbonyl, aromatic Aminothiocarbonyl, amino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, arylaminoalkyl, diarylaminoalkyl, alkylarylaminoalkyl, alkyl Amino, dialkylamino, haloalkylamino, arylamino, diarylamino, alkylarylamino, alkylcarbonylamino, alkoxycarbonylamino, aralkyloxycarbonylamino, Arylcarbonylamino, arylcarbonylaminoalkyl, aryloxycarbonylaminoalkyl, aryloxyarylcarbonylamino, aryloxycarbonylamino, alkylsulfonylamino, arylsulfonyl Fluorenylamino, heteroarylsulfonylamino, heterocyclylsulfonylamino, heteroarylthio, azide, diazenyl, -N + (R34) (R35) R36, -P (R37) 2, -P (0) (R37) 2, -0P (0) (R37) 2, -N (R38) C (0) R39, dialkylphosphonic acid group, alkylarylphosphonic acid group , Diarylphosphonic acid, hydroxyphosphonic acid, alkylthio, arylthio, perfluoroalkylthio, hydroxycarbonylalkylthio, Cyano, isothiocyano, alkylsulfinyloxy, alkylsulfonyloxy 85585 • 19- 200307684 group, arylsulfinyloxy, arylsulfinyloxy, hydroxysulfinyloxy Alkyl, sulfonylsulfonyloxy, aminosulfonyloxy, alkylaminosulfonyloxy, dialkylaminosulfonyloxy, arylaminosulfonyloxy, diarylaminosulfonyl milk Base, alkynyl arylamino, alkynyl, alkynyl, alkynyl, halofluorenyl, sulfosulfanyl, arylsulfinyl, arylsulfonyl, hydroxysulfonyl, Oxysulfonyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, arylaminosulfonyl, diarylaminosulfonyl or alkylarylaminosulfonyl Fluorenyl group; or two Q2 groups, the substituted atom system of which is or 丨, 3 arranged together to form a hypocarbyl group, an oxyalkylene group, an alkylenedioxy group, a thioalkyloxy group, or a hypochloro group. Thiolactyl; or two Q2 groups, which are substituted for the same atom and together form an alkylene group, with the proviso that if R8 is hydrogen or -0CH3, then R3 is not nitrogen, methyl, ethenyl, · 〇Ή2 (: 6Η5, -CH (CH3) C6H5, CH ( CH3) fluorenyl or _C (0) 0C2H5, with the proviso that if R3 is hydrogen, then R8 is not hydrogen, nitro, lower alkoxy, fluorenyl, or hydroxyl. 3. The compound according to item 2 of the scope of patent application, wherein R5 is hydrogen or optionally substituted alkyl. 4. The compound according to item 3 of the scope of patent application, wherein R6 is hydrogen or optionally substituted alkyl. 5. The compound according to item 4 of the scope of patent application, wherein R7 is hydrogen or optionally substituted alkyl. 6. The compound according to item s of the scope of patent application, wherein R9 is hydrogen or optionally 85585-20-20200307684 substituted alkyl. 7. The compound according to item 6 of the scope of the patent application, wherein R8 is hydrogen, optionally substituted alkyl, alkoxy, halo, pseudo-functional, -C (0) 0R23 or -OR27, where R23 is In the case of substituted alkyl, R27 is optionally substituted alkyl. 8. The compound according to item 7 of the scope of patent application, wherein R1 is optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, -CXCOR18, -0 (0) 01114, -CCCONCR15) 1116 or -CCCONCR17 Furnace Sense 15 洱 16 ο 9 · According to the compound in the scope of patent application No. 8 wherein R1 is selected from the group consisting of optionally substituted alkyl, optionally substituted aryl, and optionally substituted Heteroaryl, -C (0) 0H,-(CO) OR14 or -C (0) N (R15) R16, where R14 is optionally substituted alkyl. The compound according to item 9 of the scope of patent application, wherein R15 is optionally substituted alkyl, and R16 is hydrogen. U. Compound according to item 10 of the scope of patent application, wherein Ri is -C (〇) OH,-(CO) OR14 or -C (0) N (R15) R16, where R14 is optionally substituted alkyl. U · The compound according to item 11 of the scope of patent application, wherein Ri is _ C (0) 0CH2CH3 ^ -C (0) 0CH3 ^ -C (0) 0C (CH3) 2H &gt; -C (0) 0H ^ -c (o) och2ch2ch3, -C (0) N (H) CH3 or -C (0) NKa13. Compound according to item η of the scope of patent application, wherein Ri is isopropyl, 'nitrodongyl, 3- p sephenyl or 1-phenyl-1-ethyl. 14. The compound according to item 11 of the scope of patent application, in which R2 is nitrogen or optionally substituted -21-200307684. 15. The compound according to item 14 of the patent application, wherein R 2 is hydrogen or alkyl. 16. A compound according to item 15 of the application, wherein R2 is hydrogen. 17. The compound according to item 14 of the scope of patent application, wherein R3 is-(^ (COR10, ((OPR10, -S02 R10, or -CXC ^ NOl11 is later than 10). 18 The compound according to the scope of patent application, each of which Ri0 is independently selected from optionally substituted aryl groups, optionally substituted heteroaryl groups, optionally substituted alkyl groups, and optionally substituted aralkyl groups. 19. According to item 18 of the scope of patent application Compounds, where R1 〇, when substituted, are fluorenyl, pseudohalo, alkyl, alkoxy, alkanedioxy, haloalkyl, nitro, cyano, alkoxycarbonyl, aryl, -S02F or haloalkoxy substitution. 20. Compound according to item 17 of the scope of patent application, wherein Rii is hydrogen or optionally substituted alkyl. 21. Compound according to item 20 of the scope of patent application, wherein Rii is hydrogen. Or an alkyl group. 22. A compound according to item 21 of the patent application, wherein RH is hydrogen. 23. A compound according to item 20 of the patent application, wherein R3 is -C (0)-(optionally substituted aryl group). ), -C (0 &gt; (optionally substituted heteroaryl), -S02- (optionally substituted aryl ), -C (0)-(CH2) r-(optionally substituted aryl), where r is an integer 1-4, -C (0) 0- (optionally substituted aryl), or -C (0) N (H)-(optionally substituted aryl) 24. The compound according to item 23 of the scope of the patent application, wherein R3 is-(:( 0)-(optionally substituted aryl), Among them, the substituent on the aryl group, when present, is a dentate group, a pseudodentate group, an alkyl group, an alkoxy group, an alkanedioxy group, a haloalkane 85585 -22- 200307684 group, a nitro group, a cyano group, Carbooxycarbonyl, aryl or S02F. 25. The compound according to item 23 of the patent application, wherein R3 is -C (〇) _heteroaryl. 26. The compound according to item 23 of the patent application, wherein R3 is -S〇2 (optionally substituted aryl group), wherein the substituent on the aryl group, when present, is an alkyl group, an alkyl group, an alkoxy group, or a haloalkoxy group. 27. According to the application The compound of the scope of the patent No. 23, wherein R3 is _c (〇 &gt; (CH2 ^ _ aryl, where r is 1 or 2. φ 28. The compound of the scope of the patent, No. 23, wherein R3 is -C ( 〇) -〇- (optionally substituted aryl) 'wherein The substituent on the aryl group, when present, is halo, alkoxy or alkynyl. 29. The compound according to item 23 of the scope of patent application, wherein r3 is _c (〇) N (H) _ ( In the case of substituted aryl), the substituent on the aryl group, when present, is a phenyl group, a methoxy group, or an alkyl group. 30. The compound according to item 17 of the scope of patent application, wherein R3 is selected from _c (〇)-(4-chlorophenyl), -C (0)-(4-fluorophenyl), -C (0) _ (2-furyl), _c (0)-(2,4 -Dioxophenyl), -C (0) _ (3-nitrophenyl), -C (0)-(phenyl), _c (0)-(4-third-butylphenyl) , -S02- (4-methylphenyl), · 802- (4-third · butylphenyl), -C (0) _ (2-fluorenylphenyl), -C (〇H3 · 甲Oxyphenyl), -C (0)-(4methoxyphenyl), -C (0) _ (pinyl), -C (0) 0-phenyl, -C (0) 0_ (4-chloro Phenyl), _c (〇) 〇- (4-methoxyphenyl), -C (0) 0- (4-methylphenyl), -C (0) N (H) · phenyl, -C ( 0) N (HH4 · chlorophenyl), _C (0) N (H)-(2,4-dichlorophenyl), _C (0) N (HM4-methoxyphenyl), _C (0) N (H)-(4-methylphenyl), -C (0)-(3,4-methylenedioxyphenyl), -C (0) CH2CH2-phenyl, _S 02- (4-chlorophenyl), -S〇2_ (4-methoxy 85585 -23- 200307684 phenyl), -S〇2_ (3,4-dimethoxyphenyl), _s〇H4-tri Fluoromethoxyphenyl), -C (0)-(2,3-difluorophenyl), _c (〇H2,4-difluorophenyl), _c (〇) _ (2,5_difluorobenzyl) Group), -C (0)-(2,6-difluorophenyl), -c (0)-(3,4-difluorophenyl), _ C (0)-(3,5-difluoro Phenyl), _c (〇)-(2,3,4-trifluorophenyl), hepta (〇)-(2,3,6-trifluorophenyl), -C (0)-(2,4 , 5-trifluorophenyl), -C (〇)-(2,3,4,5-tetrafluorophenyl), • € (0) _ (2,3,4,5,6-pentafluorobenzene Group), _〇; 0) _ (2,5_bis (trifluoromethyl) phenyl), -C (〇M3,5-bis (trifluoromethyl) _phenyl), _C (0 &gt; ( 2. Trifluoromethylphenyl), -C (0)-(3-trifluoromethylphenyl), -C (0)-(4-trifluoromethylphenyl), _c (0)-( 2-fluorophenyl), -C (〇H3-fluorophenyl), -C (0)-(4-nitrophenyl), · 〇 (0)-(3-nitro-4-methylphenyl ), -C (〇H4-methoxycarbonylphenyl), -C (0)-(3-exo I: pyridyl), -C (0)-(4-pyridyl), -C (0) -(3-cyanophenyl), -C (0)-(3,4-dimethoxyphenyl), -C (0)-(2-methylphenyl), -C (0)- (4-methylphenyl ), -C (0)-(2-chlorophenyl), -C (0)-(2-fluorenyl), -C (0)-(4-biphenyl), -C (0)-( 4-fluorosulfofluorenylphenyl), -C (0) _ (3-methylphenyl), and -C (0)-(3-chlorophenyl). 31. The compound according to item Π of the application, wherein R4 is 4, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, -c (〇) 〇2G, or- c (o) n (r21) r22; where R2G is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally A substituted heterocyclic group, an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted aralkyl group, or an optionally substituted heteroaryl group, and R21 and R22 are each independently Hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted Aryl, optionally 85585 -24- 200307684, optionally substituted heteroaryl, optionally substituted aralkyl or optionally substituted heteroaralkyl, or R21 and R22 and the nitrogen atom to which they are connected, Together to form a substituted heterocyclic ring or heteroaryl ring as appropriate, 32. Compounds, where R4 is hydrogen, optionally substituted alkyl, -C (0) 0H, -C (0) 0R2G, or -C (0) N (R21) R22; where R2G is alkyl, and R21 and R22 Each is independently hydrogen, optionally substituted alkyl, or with the nitrogen atom to which they are attached, together to form a optionally substituted heterocyclic or heteroaryl ring. 33. The compound according to item 32 of the scope of patent application, wherein R4 is hydrogen, optionally substituted alkyl, _C (0) 0H, -C (0) OR2G, or -C (0) N (R21) R22; where R2 G is an alkyl group, and R2 1 and R2 2 are each independently hydrogen or an alkyl group, or form a heterocyclic ring together with the nitrogen atom to which they are attached. 34. The compound according to item 33 of the scope of patent application, wherein R4 is hydrogen, methyl, ethyl, -C (0) 〇H, -C (0) CK ethyl), -C (0) N (H) _ (Ethyl), _c (〇 &gt; hexahydropyridine · 1 · yl or -CH20-C (〇H4-fluorophenyl). 35. Compound according to item 31 of the scope of patent application, wherein r5, R6 and R7 Each is hydrogen. 36. Compounds according to item 3S of the scope of the patent application, wherein R8 is hydrogen, methoxy, chloro, iodo, fluoro, methyl, or -c (o) och2ch3. 37. According to the scope of the patent application The compound according to item 36, wherein η is 0, 1 or 2. 38. The compound according to item 1 in the scope of the application for a patent, wherein the compound is a compound of formula (11): R1 R2 85585 200307684 or a pharmaceutically acceptable derivative thereof, wherein: η is 0 to 4; A is _N (R9)-, -〇- or -S (0) t- (where t is 0 to 2) ; R1 is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted ring Alkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, -OR14, _N (R15) R16, -N (R17) N (R15) R ", _C (0) Ri8, _ φ C (0) 0R14 ^ -C (S) OR14 ^ -C (0) SR14 ^ -C ^ NCR15) R! ^. -C (0) N = NR16 4-c (o) n (r17) n (r15) r16; R2 is hydrogen or optionally substituted alkyl; or R1 and R2 and the atom to which they are connected together to form optionally substituted cycloalkyl, optionally Substituted heterocyclic group, optionally substituted aryl group, or optionally substituted heteroaryl ring; R3 is hydrogen, optionally substituted alkyl group, optionally substituted fluorenyl group, optionally substituted Alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally Substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroaryl, optionally substituted heteroaralkyl,-(:( 0) 1110, -C (0) OR10,- S (0) 2R10, CCCONCR11)! ^ », -1) N (Ι ^ 2) 111 °, -I ^ R11) (:( 0) 111 °, -N ^ 11) 0 (0) 1 ^ ( 1112 Identify 1 〇--N (Ru) C (0) N (R12) N (R13) R10 ^ -N (Rn) C (0) OR10 '-P (0) 0R10 or -p (o) (or19) or10; R4 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally 85585 -26- 200307684 substituted miscellaneous Aryl, optionally substituted soil alkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, -C (0) R18, -C ( 0) 0R2 (), -C (0) N (R2i) r22 or -C (0) N (R42) N (R21) R22; R5, R6 and R7 are each independently hydrogen, optionally substituted alkyl, Optionally substituted aralkyl, optionally substituted heteroaralkyl, -〇R14, -S (0) 2R14, -N (R15) R16, -C (0) R18, -C (0) 0R20 Or -C (0) N (RU) R2 2: or R4 and R7, or R4 and R5, or R4 and R6, or R5 and R7, or r5 and R6 Or R6 and R7 together form a cycloalkyl group optionally substituted, a heterocyclic group optionally substituted, or a cyclofluorenyl ring optionally substituted; and other R4, R5, R6 and R7 are as described above; or R4 Together with R5 to form a keto group; and r6 and R7 are both as described above; or R6 and R7 are together to form a keto group; and R4 and R5 are as described above; each R8 is independently selected from the group consisting of hydrogen, optionally substituted alkyl , Optionally substituted fluorenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, drawing group, pseudo group, cyano, nitro, -C ( 0) 0R23, -C (0) N (R24) R25, -C (0) R26, -OR27, and N (R28) R29; R9 is hydrogen, optionally substituted alkyl or -S (0) 2 R4 3; R10, R11, R12, R13, and R19 are selected from ⑻ or (b) below. (A) Ru, R12, R13, and R19 are each independently hydrogen, optionally substituted alkyl, or Optionally substituted fluorenyl, optionally substituted alkynyl, optionally substituted cycloalkynyl, optionally substituted aryl, optionally substituted 85585 -27- 200307684 aralkyl, optionally Substituted heterocyclyl, Optionally substituted heteroaryl or optionally substituted heteroaralkyl; and r1g is optionally substituted alkyl, optionally substituted fluorenyl, optionally substituted alkynyl, optionally substituted Cycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; or (B) R1G and R11, and / or R10 and R12, and / or R10 and R13, and / or R1G and R19, and / or R11 and R12, and / or R12 and R13, and the atoms to which they are connected, Together form an optionally substituted heterocyclic ring or an optionally substituted heteroaryl ring; and other Ri0, Rii, R12, R13 &amp; R19 are selected as in ⑻ above; R14, R15, R16 and R17 are in If ⑻ or (b) is selected ... ⑻ R14, R15, R16 and R17 are each independently 氲, optionally substituted alkyl, optionally substituted fluorenyl, optionally substituted alkynyl, optionally substituted Cycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally A substituted heteroaryl or optionally substituted heteroaralkyl; or (b) R15 and R16 and the nitrogen atom to which they are attached together to form a optionally substituted heterocyclyl ring or optionally substituted Heteroaryl ring, and R14 and R17 are selected as above, R18 is optionally substituted alkyl, optionally substituted amidyl, optionally substituted alkynyl, optionally substituted ring Alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; 85585- 28- 200307684 R20, R21, R22 and R42 are selected from ⑻ or (b) as follows: ⑻R20, R21, R22 and R42 are each independently hydrogen, optionally substituted alkyl, or optionally substituted 晞Base, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aryl group, optionally substituted heterocyclyl, optionally substituted Heteroaryl or optionally substituted heteroaralkyl; or (b) R21 and R22 are connected to each other The nitrogen atoms connected together form a heterocyclic ring optionally substituted or a heteroaryl ring optionally substituted, and R20 and R42 are selected as in ⑻ above; R23, R24, R25 and R26 are in Choose from the following ⑻ or ⑼: ⑻R23, R24, R25, and R26 are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted Cycloalkyl, optionally substituted aryl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; or (B) R24 and R25 and the nitrogen atom to which they are attached together form a heterocyclic ring optionally substituted or a heteroaryl ring optionally substituted, and R2 3 and R2 6 are selected as above ; R27, R28, and R29 are selected from ⑻ or 下述 as follows: ⑻ 圮 7;; ^ 8 and R29 are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, and optionally Substituted alkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted Heteroaryl, optionally substituted heteroaralkyl, -C (0) R3 G, -C (0) 0R3 1 or -C (〇) N (R3 2) R3 3; 4 (b) R28 and R29 And the nitrogen atom to which they are connected, together with the optionally substituted heterocyclic ring or the optionally substituted heteroaryl ring, and R27 is selected from the above ⑻ as in 200307684; R3 0 is hydrogen, as appropriate Substituted alkyl, optionally substituted amidino, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally Substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; R31 is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkyne Base, optionally substituted cycloalkyl, optionally substituted φ, aryl substituted, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted For substituted heteroaryl groups, R32 and R33 are selected from ⑷ or (b) as follows: ⑻R32 and R33 are each independently hydrogen, optionally substituted alkyl, or Optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aryl group, optionally substituted heterocyclic group, Optionally substituted heteroaryl or optionally substituted _heteroaralkyl; or (b) R32 and R33 and the nitrogen atom to which they are attached together to form a optionally substituted heterocyclic group or optionally Substituted heteroaryl ring; R43 is optionally substituted alkyl, optionally substituted fluorenyl, optionally substituted decyl, optionally substituted alkynyl, optionally substituted aryl, Optionally substituted aryl groups, optionally substituted heterocyclic groups, optionally substituted heteroaryl groups, or optionally substituted heteroaralkyl groups; each of R1 to R33, R42 and R43 when substituted 'Is substituted by one or more substituents each of 85585 -30- 200307684 selected from Q1; Q1 is i group, pseudo group, hydroxyl group, keto group, thio group, nitrile, nitro group, formyl group, mercapto group , Hydroxycarbonyl, hydroxycarbonylalkyl, alkyl, haloalkyl, polyhaloalkyl, aminoalkyl, diaminoalkane , Alkenyl groups containing 1 to 2 double bonds, block groups containing 1 to 2 reference bonds, cycloalkenyl, cyclohexyl antiyl, heterocyclyl, heterocyclylalkyl, aryl, heteroaryl, Aryl, aryl, aryl, alkynyl: aryl, heteroaryl, aryl, triphenyl, triphenyl, dialkyl, alkyl, diaryl, triaryl, alkyl, aryl Alkylene, carbonyl, cycloalkyl, heterocyclyl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, alkoxycarbonylalkyl, aryloxycarbonyl, aryloxycarbonylalkyl, Aryloxycarbonyl, aralkyloxycarbonyl, arylcarbonylalkyl, aminocarbonyl, alkylaminocarbonyl, dialkylamino, arylaminocarbonyl, diarylaminocarbonyl, aralkyl Aminoaminocarbonyl, alkoxyaryloxy, heteroaryloxy, heteroarylalkoxy, heterocyclyloxy, cycloalkyloxy, perfluorooxo, fluorenyloxy, decyloxy, aromatic Carbooxy, alkylcarbonyloxy, arylcarbonyloxy, aralkylcarbonyloxy, carbooxycarbonyloxy, aryloxycarbonyloxy, aralkyloxycarbonyloxy, aminocarbonyloxy, alkyl amine Carbonyloxy, dialkylaminocarbonyloxy, arylarylaminocarbonyloxy, diarylaminocarbonyloxy, guanidine, isothioureido, formamyl, alkylformamyl, aryl Formamyl, aminothiocarbonyl, alkylaminothiocarbonyl, arylaminothiocarbonyl, amine, aminoalkyl, alkylamino, dialkylamino, arylamino, diaryl Alkylamino, alkylarylaminoalkyl, alkylamino, dialkylamino, alkylamino, arylamino, diarylamino, alkylarylamino, alkylcarbonylamine Group, 85585 -31- 200307684 alkyloxycarbonylamino, aralkyloxycarbonylamino, arylcarbonylamino, arylcarbonylaminoalkyl, aryloxycarbonylaminoalkyl, aryloxyarylcarbonyl Amino group, aryloxycarbonylamino group, alkylsulfonylamino group, arylsulfonylamino group, heteroarylsulfonylamino group, heterocyclylsulfonylamino group, heteroarylthio group, Azide, diazonium, -N + (R34) (R35) R36 ... p (R37) 2, -P (0) (R37) 2, -〇P (〇) (R3 7) 2, -N ( (K38) (:; (0) K39, dialkylphosphonic acid group, arylarylphosphonic acid group, diarylphosphonic acid group, hydroxy Phosphono, alkylthio, arylthio, perfluoroalkylthio, hydroxycarbonylalkylthio, thiocyano, isothiocyano, alkylsulfinyloxy, alkylsulfonyl Oxy, aryl sulfonyloxy, arylsulfonyloxy, hydroxysulfonyloxy, alkoxysulfonyloxy, aminesulfonyloxy, aminesulfonyloxy, diamine Benzylamino ~ fluorenyloxy, arylaminosulfonyloxy, diarylaminosulfonyloxy, arylarylsulfonyloxy, sulfonylsulfonyl, alkylsulfinyl, alkyl %% fluorenyl, arylsulfinyl sulfonyl, arylsulfonyl sulfonyl, hydroxysulfonyl, oxo% fluorenyl, amine sulfonyl, sulfonyl sulfonyl, sulfonyl sulfonyl , Arylaminosulfonyl, diarylaminosulfonyl or alkylaryl-amine amine hindering group; or two Q1 groups, the substituted atom system of which is in the order of 丨, 2 or 丨, 3, Together form an alkylene, oxyalkylene, alkylenedioxy, thioalkyloxy or sulfinyldithiooxy group, or two Q1 groups, which are substituted for the same atom and together form an alkylene oxide R, r35 & r36 are each independently hydrogen, alkyl, aromatic Aryl, aralkyl, heterowanyl, heteroaralkyl, heterocyclyl or heterocyclylalkyl; R37 is aryl, alkoxy, aralkoxy, alkyl, heteroaryl, heterocycle 85585- 32- 200307684 group, aryl or -NR4OR4i; R4G and R41 are each independently hydrogen, alkyl, aralkyl, aryl, heteroaryl, heteroaralkyl or heterocyclic group, or R4G and R41 together Forms an alkylene, nitroalkylene, oxyalkylene, or thioalkylene group; R38 is hydrogen, alkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, or heterocyclyl Alkyl; and R3 9 is an alkoxy group, an arylalkyl group, an alkyl group, a heteroaryl group, a heterocyclic group, an aryl group, or -N (R4G) R41; each Q1 is independently unsubstituted, or is Or more than two substituents each independently selected from Q2; each Q2 is independently a radical, a pseudofunctional group, a mesityl group, a keto group, a thio group, a nitrile, a nitro group, a methyl group, a fluorenyl group, a hydroxycarbonyl group, a hydroxy group Carbonylalkyl, alkyl, haloalkyl, polyalkyl, aminoalkyl, diaminoalkyl, fluorenyl containing 1 to 2 double bonds, block containing 1 to 2 reference bonds, ring Alkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl , Aryl, heteroaryl, aralkyl, aralkyl, arylalkynyl, heteroaralkyl, trialkylsilyl, dialkyl square radical, trisyl-1, square radical, triaryl fragment Alkyl, alkylene, arylalkylene, alkylcarbonyl, cycloalkylcarbonyl, heterocyclylcarbonyl, square carbonyl, heteroarylcarbonyl, alkoxycarbonyl, alkoxycarbonylalkyl, aryloxycarbonyl, Aryloxycarbonylalkyl, aralkyloxycarbonyl, aralkyloxycarbonyl, arylcarbonylalkyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl, diaryl Aminocarbonyl, aralkylaminocarbonyl, oxyaryloxy, heteroaryloxy, heteroaryloxy, hetero85585 -33- 200307684 cyclooxy, cycloalkoxy, perfluoroalkoxy , Alkenyloxy, decyloxy, aralkoxy, alkcarbonyloxy, arylcarbonyloxy, aryloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, aralkyl * oxy Fluorenyloxy, aminocarbonyloxy, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylarylaminocarbonyloxy, diarylaminocarbonyl Oxygen, guanidine, isothiourea, formamyl, alkylformamyl, arylmethane, aminethiocarbonyl, alkylaminothiocarbonyl, arylaminothiocarbonyl, amine, aminoamino , Alkylaminoalkyl, dialkylaminoalkyl, arylaminoalkyl, diarylaminoalkyl, alkylarylaminoalkyl, alkylamino, dialkylamino, haloalkyl Amine, arylamino, diarylamino, alkylarylamino, sulfanylamino, alkoxycarbonylamino, aralkyloxycarbonylamino, arylcarbonylamino, arylcarbonylamine Alkyl, aryloxycarbonylamino, aryloxyarylcarbonylamino, aryloxycarbonylamino, alkylsulfonylamino, arylsulfonylamino, heteroarylsulfonyl Aminoamino, heterocyclic sulfoamidoamino, heteroarylthio, azide, diazino, -n + (r34) (r35) r36, -P (R37) 2, _p (〇) ( R37) 2, · ορ (ο) (γι37) 2, -N (R38) c (o) R39, dialkylphosphonic acid group, alkylarylphosphonic acid group, diarylphosphonic acid group, hydroxyphosphine Acid, alkylthio, arylthio, perfluoroalkylthio, hydroxycarbonylalkylthio, thiocyano, isothiocyanate, Alkylsulfinyloxy, alkylsulfinyloxy, arylsulfinyloxy, arylsulfinyloxy, hydroxysulfinyloxy, sulfonyloxy, amine "Oxy, Wan" amine-based aryloxy group, di-burned amine-based aryloxy group, arylamino-based carboxylic acid group, di-squared-amine-based carboxylic acid group, aryl-based amine group carbonyl group, Alkylidene, halofluorenyl, alkylsulfonyl, arylsulfinyl, arylsulfonyl, hydroxyl 85585 -34- 200307684 sulfonyl, alkoxysulfonyl, amine Sulfonyl, alkylaminosulfonyl, monoalkylamino% fluorenyl, arylaminosulfonyl, diarylaminosulfonyl or alkylarylaminosulfonyl; or two Q2 groups Group in which the substituted atom system is arranged in a 丨, 2 or u group, and together form an alkylene group, an oxyalkylene group, an alkylenedioxy group, a thioalkyloxy group or an alkylenedithio group; or Each Q2 group is substituted by the same atom to form an alkylene group, with the proviso that if R8 is hydrogen or -0CH3, then R3 is not hydrogen, methyl, ethyl, -ch2c6h5, -ch (ch3 ) c6h5, ch (ch3) fluorenyl or -C (0) 0C2H5, With the proviso that, when R3 is hydrogen, then R8 is not hydrogen, a nitro group, a lower alkoxy group, a hydroxyl group or a tooth. 39. The compound according to item 38 of the scope of patent application, wherein: η is 0 or 1; A is -N (R9)-; R1 is optionally substituted aryl or -C (0) 0R14; R2 is hydrogen or Optionally substituted alkyl; R3 is hydrogen, -CCCOR1 G or -S (0) 2 R10; R4 is hydrogen, optionally substituted alkyl or -c (o) or2〇; R5, R6, R7 and R9 is each hydrogen or optionally substituted alkyl; R8 is chlorine or -OR2 7; each R1 G is independently an optionally substituted alkyl, optionally substituted aryl, or optionally substituted arane R14 is optionally substituted alkyl; and 85585 -35- 200307684 R27 is optionally substituted alkyl. 40. The compound according to item 39 of the scope of patent application, which is selected from the group consisting of the following: (3,4-monofluoro-allyl)-(1 · phenyl-1,3,4,9-tetrahydrocarin_ 2-yl) methanone 2- (4-fluoro-aspartyl) -2,3,4,9-tetrahydro-111- / 8-indolin ethyl acetate 2- (3 + difluoro- Benzamidine) _2,3,4,9_tetrahydrocarboline-μcarboxylic acid ethyl 2- (3,4-difluoro_benzoate) _4,4_dimethyl_2,3,4 , 9-tetrahydro_1 fast stone-Ye Lin-1 · ethyl carboxylate 2- (4-fluoro-benzyl) -4,4-dimethyl-2,3,4,9_tetrahydro -111- / 3-carbene-1-carboxylic acid ethyl ester 41. The compound according to item 2 of the scope of patent application; wherein: η is 0 or 1; A is -N (R9)-; R1 is -C (0 OR14; R2 is hydrogen; R3 is hydrogen, optionally substituted alkyl, optionally substituted aryl, optionally substituted aralkyl, or optionally substituted heteroaralkyl; R4 is hydrogen, -(3 (0) 1118, -C (0) 0R2. Or -c (o) n (r21) (r22); R5, R6 and R7 are each independently hydrogen or optionally substituted alkyl; R8 is hydrogen , Optionally substituted alkyl, optionally substituted aryl, halo or -OR27; R9 is hydrogen or optionally substituted alkyl; R14 is hydrogen or optionally Substituted alkyl; R18 is optionally substituted heterocyclic group; R2G is hydrogen or optionally substituted alkyl; 85585 -36- 200307684 R2 1 and R2 2 are each independently a substituted alkyl group, Or R2 1 and R2 2 and the nitrogen atom to which they are attached together to form a heterocyclic ring optionally substituted; and R27 is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted Alkynyl or optionally substituted aralkyl. 42. The compound according to item 41 of the scope of patent application, which is selected from the group consisting of the following: 9-bromo-1,2,3,6_tetrahydro-nitrogen Ethyl [4,5 hepta] eardol-5-chitoate 3-eridine · 2 · ylmethyl · 1,2,3,6 · tetrahydro-nitrogeno [4,5_bH indole-5-chi Ethyl Acetate 3 · Cyclohexylmethyl · 1,2,3,6-tetrahydro · nitrogeno [4,5_b] indole-5-benzyl ethyl 3-benzyl-1,2,3,6 _Tetrahydro-nitrogeno [4,5Hepta] indole-5-carboxylic acid ethyl ester 43. The compound according to item 40 of the scope of patent application, which is selected from the group consisting of: 1,1_dimethyl_ 1,2,3,6 · tetrahydronitrogen hydride [4 &b;b; ethyl carboxylate]; and 1,1,3,6-tetramethyl_1,2,3,6_tetrahydro Nitrogen entrains [4,5VII] 啕Indole-5_carboxylic acid ethyl ester 44. The compound according to item 2 of the scope of patent application; wherein: η is 0 or 1; A is -N (R9)-; R1 is -C (0) 0R14; R2 is hydrogen ; R3 is -C (0) R10; R4 is hydrogen or -C (0) OR2; R5, R6 and R7 are each hydrogen; optionally substituted aryl R8 is hydrogen, optionally substituted alkyl, Halo or -OR27; R9 is hydrogen; 85585 -37-200307684 R1 0 is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted cycloalkyl, optionally substituted aromatic Base, optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; R14 is optionally substituted alkyl, optionally substituted fluorenyl, optionally Substituted alkyne: base or optionally substituted alkynyl 'R20 is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, or optionally substituted aralkyl And R27 is an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted block group, or an optionally substituted aromatic group. 45. The compound according to item 44 of the scope of patent application, which is selected from the group consisting of the following: 3- (3-phenylpropanyl) -1,2,3,6-tetrahydronitrogeno [4,5-b ; N-dodecyl-5-carboxylic acid isopropyl ester; 3-Ethylfluorene 9- (4 · methoxyphenyl) -1,2,3,6-tetrahydroazepine [4,5Hepta] indole -5-Ethyl carboxylic acid; and 3-Ethyl-8-bromo-1,2,3,6_tetrahydronitrocarba [4,5-b] Homo-2,5_dicarcoic acid Diethyl ester; 46. Compound according to item 2 of the scope of patent application; wherein: η is 0 or 1; A is -N (R9)-; R1 is -C (0) 0R14; R2 is hydrogen; R3 is (( 0) 1110; R4 is hydrogen, optionally substituted alkyl, optionally substituted aryl 85585 -38- 200307684 or _. (〇 辉 2〇; R5, R6 and R7 are each independently hydrogen or optionally Substituted alkyl; R8 is hydrogen, optionally substituted alkyl,-or -OR27; R9 is hydrogen; R1G is optionally substituted aryl; Rl4 is optionally substituted alkyl, as appropriate Substituted alkenyl, optionally substituted alkynyl, or optionally substituted aralkyl; R20 is optionally substituted alkyl, optionally substituted fluorenyl, optionally substituted Alkynyl or optionally substituted aralkyl; and R21 is optionally substituted alkyl. 47. The compound according to item 46 of the scope of patent application, which is selected from the group consisting of the following: 3. (4-p-methoxy Benzamidine) -1-methyl · 1,2,3,6-tetrahydronitrogeno [4,5Hepta> 5 丨 indole-5-carboxylic acid ethyl ester; 3 -Methyl-1,2,3,6-tetrahydronitrogeno [4,5-b] indole-5-carboxylic acid ethyl ester; 3- (4-p-methoxybenzyl) -1,1 -Dimethyl-1,2,3,6-tetrahydroazepine [4,5 hepta] indole-5-carboxylic acid ethyl ester; and 1,1-dimethyl-3-sunflower fluorenyl-1 , 2,3,6-tetrahydronitropyrene [4,5-b; H 丨 indole-5 · carboxylic acid ethyl ester. 48. Compounds according to item 2 of the scope of patent application; wherein: η is 0 or 1; Α is _N (R9)-; R1 is optionally substituted heterocyclic group, &lt; (0) 01114, -0: (8) 01114, -qCOSRM'-CCCONCR ^ RH-CCCONsNRba-CCCONCR ^ NCR15 ^ 16; 85585 -39- 200307684 R2 is hydrogen; R3 is -C (0) R10; R4 Hydrogen, optionally substituted alkyl, -C (0) R18, _C (0) OR2G, or -C (0) N (R21) R22; each of R5, R6, and R7 is independently hydrogen or optionally substituted Alkyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, -0 & 14, -S (0) 2R14, -N (R15) R16, -C (0) R18,- C (0) 0R2 () or -C (0) N (Rn) R22; or R6, together with R7 and the carbon to which they are attached, together form a substituted heterocyclic group, or together form a keto group, and R5 is as described above; R8 is hydrogen, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, halo, -C (0) OR23, -OR27, or -N ( R28) R29; R9 is hydrogen or optionally substituted alkyl; R1G is phenyl and is substituted by one or more Q1 groups selected from the group consisting of halo, pseudo group, 1¾ tiger group or multiple self-burning groups ; R14, R15, R16 and R17 are each independently hydrogen, optionally substituted alkanyl, optionally substituted alkenyl, optionally substituted cycloalkane , Optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl or optionally substituted heteroaralkyl; or R15 and R16 and the nitrogen atom to which they are connected, Together form an optionally substituted heterocyclyl ring, and R14 and R17 are as described above; or R18 is optionally substituted alkyl; r20, R21 and R22 are each independently hydrogen or optionally substituted alkyl; R23 is optionally substituted alkyl; 85585 -40- 200307684 R27, R28 and R29 are each independently hydrogen, optionally substituted alkyl, optionally substituted aralkyl, _C (0) R3G, -C (0) 0R3 1 or -C (0) N (R3 2) R3 3; R3 0 is optionally substituted alkyl, optionally substituted aryl, or optionally substituted heterocyclic group; R31 is deemed Optionally substituted alkyl, optionally substituted aryl, or optionally substituted aralkyl; and R32 and R33 are each independently hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, Optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heteroaryl Or the optionally substituted heteroaralkyl; or R33 and R32 together with the nitrogen of their attached, together form an optionally substituted heterocycle or of the optionally substituted heteroaryl ring. 49. The compound according to item 2 of the scope of patent application; wherein: η is 0 or 1; A is -N (R9)-; R1 is optionally substituted heterocyclic group, -C (0) 0R14, -C ( 0) N (R15) R16 aC (0) N (R17) N (R15) R16; R2 is nitrogen; R3 is -C (0) R10; R4 is hydrogen, optionally substituted alkyl, _C (0) R18 or -C (0) N (R21) R22; each of R5, R6 and R7 is independently hydrogen, optionally substituted alkyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, -〇 化 14, -S (0) 2R14, -N (R15) Ri6, -C (0) R18, -C (0) OR2〇 or -C (0) N (R21) R22; R8 is hydrogen, depending on Case substituted alkyl, optionally substituted aryl-41- 85585 200307684, optionally substituted heteroaryl, _ group; R9 is hydrogen or optionally substituted alkyl; R10 is phenyl, is One or more qi groups selected from the group consisting of halo, pseudo-, self-fired or multi-fired; R14, R15, R16, and R17 are each independently hydrogen, optionally substituted alkyl, or Optionally substituted alkenyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted Heteroaryl or optionally substituted heteroaralkyl; or R15 and R16 and the nitrogen atom to which they are attached together to form a optionally substituted heterocyclic ring, and R14 and R17 are as described above; or R18 Is optionally substituted alkyl; R20, R21 and R22 are each independently hydrogen or optionally substituted alkyl; R23 is optionally substituted alkyl; R27, R2 8 and R29 are each independently hydrogen, as appropriate Substituted alkyl, optionally substituted aralkyl, -C (0) R3G, -C (0) 0R31, or -C (0) N (R32) R33; R3G is optionally substituted alkyl, Optionally substituted aryl or optionally substituted heterocyclic; R3 1 is optionally substituted alkyl, optionally substituted aryl or optionally substituted aralkyl; and R3 2 and R33 Each independently hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally Substituted heteroaryl or optionally substituted heteroaralkyl; or R3 2 and R3 3 and the nitrogen to which they are attached together to form a optionally substituted 85585 -42- 200307684 heterocyclic ring or optionally substituted heteroaryl ring. 50. The compound according to item 49 of the scope of patent application, which is selected from the group consisting of the following: 3_ (3,4_difluorobenzyl) _methyl_q, 2,3,6_tetrahydronitrogen [ 4,5Hepta] Ethyl hydrazine-5-chinoic acid; difluorobenzyl)) _ 1,1_dimethyl · 1,2,3,6-tetrahydronitrogen [4,5-b] Indole-5-carboxylic acid ethyl ester; 3- (3,4-monomurylbenzyl) _1,1_dimethyl-1,2,3,6-tetrahydronitropyre [4,5_b] Indole-5-carboxylic acid isopropyl ester; _ 3 · (3,4-difluorobenzyl) small methyl-; ι, 2,3,6-tetrahydronitrogen [4,5 七] Isoline-5-isopropyl isopropyl ester; 3- (3,4-difluorobenzylidene) -2-methyl-1,2,3,6-tetrahydronitrogen [4,5 七] Benzole-5-cyclobutyridamine; 3- (3,4-difluorobenzylidene) -1_methyl · ι, 2,3,6-tetrahydronitrogen [4,5- b] 4 丨 Indole-5_carboxylic acid cyclobutylammonium amine; polyisobutyl ^-(3,4-difluorocarbamyl) -1,1_dimethyl-1,2,3,6 -Tetral ML Moxa and [4,5-b] indole-5-carboxamidine; 3- (4-chlorobenzyl) -1-methyl-1,2,3,6- Tetrahydronitrogero [4,5Hepta] indole-5-carboxylic acid ethyl ester; 3- (4-chlorobenzylidene) -1,1-dimethyl-1,2,3,6- Tetrahydronitrogens engulf [4,5 七] 4丨 Homo-5-acrylic acid ethyl ester; 3 · (4-fluorobenzylidene) -small methyl-i, 2,3,6-tetrahydronitrogeno [4,5Hepta] indole-5-carboxy Acid ethyl ester; 3 (4-fluorobenzyl) -2-methyl-1,2,3,6-tetrahydronitrogeno [4,5 hepta] indole-5-carboxylic acid n-propyl ester ; And 85585 -43- 200307684 3 &lt; 4-Fluorobenzyl) -2-methyl-1,2,3,6 · tetrahydronitro, which infers [4,5 hepta] indole-5-carboxylic acid cyclobutylphosphoniumamine. 51. The compound according to item 2 of the scope of the patent application; wherein η is 0 or 1; eight is _specific 9)-; R1 is optionally substituted heterocyclic group, -C (0) 0R14, -c ( o) n (r15) r16 4-c (o) n (r17) n (r15) r16; R2 is hydrogen; R3 is -C (0) R10; R4 is hydrogen, optionally substituted alkyl, -CXCOR18 Or -C (0) N (R21) R22; each of R, R and R is independently nitrogen, optionally substituted alkyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, _ 〇1 ^ 4, -S (0) 2R14, -N (R15) R16, -C (0) R18, -c (o) or20 or _c (o) n (r21) r22; R8 is _C (0 ) 0R23, -OR27 or -N (R28) R29; R9 is hydrogen or optionally substituted alkyl; R1 G is phenyl, substituted by one or more Ql groups selected from the following: halo, R14, R15, R16 and R17 are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted cycloalkyl, optionally Substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; or R15 and R16 and the nitrogen atom to which they are attached, Optionally form a heterocyclic ring, and R14 and Ri7 are as described above; or R18 is optionally substituted alkyl; 85585 -44- 200307684 R20, R2 1 and R22 are each independently hydrogen or optionally Substituted ^ 'R23 is optionally substituted alkyl; optionally substituted alkyl, as -C (0) 0R31 or _c (0) n (r32) r33; optionally substituted aryl Or R27, R28, and R29 are each independently hydrogen, optionally substituted aryl, ((O) R3 0, R30 is optionally substituted alkyl, and optionally substituted heterocyclic group; R3 1 is optionally Substituted alkyl, optionally substituted aryl, or optionally substituted aralkyl; and R32 and R33 are each independently hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally Optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; or R32 and R33 and each other Waiting for the connected nitrogen to form an optionally substituted heterocyclic ring or an optionally substituted heteroaryl ring together. 52 · According to the application The compound of claim 51, which is selected from the group consisting of the following: 8-Dimethylamino-3- (4-fluorobenzylidenedimethyl_i, 2,3,6-tetrahydronitrogen [4,5-b] indole-5-carboxylic acid ethyl ester; 8-[(2-chloroethyl) methylamino] -3- (4-fluorobenzylfluorenyl) _i, i_difluorenyl _i, 2,3,6-tetrahydronitrogen benzo [4,5-bH indole-5-carboxylic acid ethyl ester; 8- (3,3_-methylmethyl) -3- (4-benzylbenzene (Methylamidino) _ι, ι_dimethyl_ι, 2,3,6-tetrahydronitrogeno [4,5hepta] indole-5-carboxylic acid ethyl ester; H4-fluorobenzyl))- 1,1-Dimethyl dong [methyl (tetrahydropyrrole carbonyl) amino hydrazone, 2,3,6_tetrahydronitrogeno [4,5 hepta] indolecarboxylic acid ethyl alcohol; 3- (4 -Fluorobenzylidene group> U_dimethyl_8_ (trimethylureido) -tetrahydro 85585 -45- 200307684 nitrogen benzo [4,5-b] Whdo-5_carboxylic acid ethyl ester; 3- (4-fluoromonomethylamidodimethyl) [methyl (morpholin 4-lanyl) amino] -1,2,3,6-tetrahydronitropyre [4,5-b] Indole · 5-carboxylic acid ethyl ester; 3- (4-fluorobenzylidene) _ΐ, ι_dimethyl_8_ (hexahydropyridine small carbonyloxy) &gt; 1,2,3,6_tetrahydro Nitrogen [4,5-b; N indole-5-carboxylic acid ethyl alcohol; 3- (4-fluorobenzyl) -1,1-dimethyl each (4_ Methylhexahydropyridine-μ-aminocarbamyloxy) -1,2,3,6-tetrahydronitrocarba [4,5H &gt;? 丨 Homo-5-acrylic acid ethyl ester; 3- (4 · Fluorobenzyl) -i, i-dimethyl each phenethylamine formamyloxy-Lu 1,2,3,6-tetrahydronitrogeno [4,5hepta] pyridine Ethyl-5-carboxylic acid; 3- (4-fluorobenzylidene) -1,1-dimethyl each thiophen-2-ylmethylamine formamyloxy) 1,2,3 , 6-Tetrahydronitrogero [4,5-b] indole-5-acrylic acid ethyl ester; 3- (4-fluorobenzylidene) -1,1-dimethyl-8- (furan- 2-ylmethylamine formamyloxy) -1,2,3,6-tetrahydronitrocarba [4,5-bH 丨 indole-5-carboxylic acid ethyl ester; 3 · (4-fluorobenzyl Fluorenyl) -1,1-dimethyl · 8 · (μmethyl-3-pyridin-2-yl-ethylureido) -1,2,3,6-tetrahydronitropyrene [4,5 -b] indox-5_chinoic acid ethyl ester; 8- (4-fluorobenzylmethylamino) -3- (4-fluorobenzyl) -1,1-dimethyl-y1 , 2,3,6-tetrahydronitrogen appeals to [4,5Hepta] stilbene-5-carboxylic acid ethyl ester; 8- (3.Phosyl-1-methylmethyl) -3- (4_ Fluorobenyl) -1,1-dimethyl-1,2,3,6-tetrahydronitrogen [4,5 七] qiao 丨 Homo-5-acrylic acid ethyl ester; 3- (4- Fluorobenzyl) _1,1_dimethyl-8_ (1-methyl-3- Pyridin-2-ylmethylureido) -1,2,3,6-tetrahydronitrocarbazone [4,5-b] indole-5-carboxylic acid ethyl ester; 8-cyclobutylaminomethylamino Oxy-3--3- (4-fluorobenzylidene) _1,1-dimethyl-1,2,3,6-tetrahydronitrocarba [4,5Hepta] indole-5-carboxylic acid ethyl ester ; 8-Cyclopentylamine formamyloxy-3- (4-fluorobenzyl amidino) -1,1-dimethyl_ 85585 -46- 200307684 1,2,3,6-tetrahydroazepine Ethyl [4,5_b] Windole-5-acrylic acid ethyl ester; 8-cyclohexylamine methyloloxy-3- (4-fluorobenzylfluorenyl) _ι, ι_dimethyl_1,2, 3,6-tetrahydronitropyre [4,5_b] indole-5 · carboxylic acid ethyl ester; 3- (4-fluorobenzyl) -1,1-dimethyl-8- (5-methyl P-pyridine_2_ylmethylamine formamyloxy) -1,2,3,6-tetrahydronitrogeno [4,5-b] indole-5_carboxylic acid ethyl ester; 3- (4-fluorobenzyl) -1,1-dimethyl-8-methylaminomethyl || yloxy_ 丨, 2,3,6_ tetrahydronitrogeno [4,5-b] 啕Indole-5-carboxylic acid ethyl ester; 3- (4-fluorobenzoate) -1,1-dimethyl-8-isopropylamine methylaminooxy-1,2,3,6-tetrahydro Nitrogen [4,5-b; N-Hydroxy-5-acrylic acid ethyl ester; 8-(-nitrotetrafluoren-1-carbonyloxy) -3- (4-fluorobenzyl) -yl, μdimethylformate 1,2,3,6-tetrahydronitrogen Homo [4,5_b] pyrene-5_acrylic acid ethyl ester; 3_ (4_fluorobenzylidene) -1,1-dimethyl-8- (4 • pyridine_2_yl-hexahydropyridine Phen-1-carbonyloxy) _1,2,3,6_tetrahydroazepine and [4,5_b] indox-5-acrylic acid ethyl ester; 8-cyclopropylamine formamyloxy-3 -(4-fluorobenzylidene) -i, i-dimethyl-1,2,3,6-tetrahydronitrocarba [4,5 七] 沔 | Homo-5-acrylic acid ethyl ester; 8 · (Ethyl (isopropyl) aminomethylamidoxy) -3- (4-fluorobenzylidene) -1,1-dimethyl-1,2,3,6-tetrahydronitrogen [4,5-b] indyn-5_carboxylic acid ethyl ester; 3- (4-fluorobenzylidene) -1,1_dimethyl_8- (pyridin-2-ylmethylamine formamidine Alkoxy) -1,2,3,6-tetrahydrazine azeo [4,5-1)] 4 丨 -5_resonate ethyl ester; 3- (3,4-monofluoroaspartate) -1,1,6-trimethyl_1,2,3,6_tetrahydrogen entrains [4,5-b] indole-5-carboxylic acid ethyl ester; 3- (4-fluorobenzylfluorenyl) ) -1,1_dimethyl_8_ (pyridylmethylamine formamyloxy H, 2,3,6-tetrahydronitrogeno [4,5-bH indol-5_carboxylic acid ethyl ester; 8-ethoxyweilyloxy-3- (4-fluorobenzoate dimethyl-1,2,3,6-tetrahydro 85585 -47- 200307684 nitrogen nitrogen [4,5 hepta] indole-5 -Ethyl double acid; 3- (4-fluorobenzene (Acid group) -1,1-dimethyl each (tetrahydro-exocarbon_ι_carboxyoxy) -1,2,3,6-tetrahydronitrogen ac [4,5 七] 沔 | 声 -5 -Ethyl hexanoic acid; 8-diethylaminemethylamidooxy-3- (4-fluorobenzylamido η, ι-dimethyl-1,2,3,6-tetrahydronitrogen [4,5-b] Indole-5-carboxylic acid ethyl ester; 8-dimethylamine formamyloxy-3- (4-fluorobenzyl dimethyl-1,2,3,6 -Tetrahydronitrogeno [4,5Hepta] indole-5-acetic acid ethyl ester; 3- (4 • fluorobenzylidene) -1,1-dimethyl-8 · (morpholinoline carbonyl (Oxy)-1,2,3,6-tetrahydroazepine level [4,5-b] e 丨 Homo-5-carboxylic acid ethyl cool 8_ diisopropylamine formyloxy-3 -(4-fluorobenzylidene) -1,1-dimethyl-1,2,3,6-tetrahydronitrogeno [4,5-pentole-5-chinoic acid ethyl ester; 3- ( 4-fluorobenzylidene) -1,1-dimethyl-8- (4-methyl-hexahydrou ratio 1 ^ well-1-hexyllactyl) _1,2,3,6_tetrahydro Nitrogen [4,5-b] indole-5-acetic acid ethyl ester; 3- (4-Gabenzoate) -1,1-dimethyl-8_ (2-fluorenyl flavor Junlin- 1-Tanyllactyl) _1,2,3,6 · tetrahydronitrogeno [4,5_b] indole-5 · carboxylic acid ethyl ester; 3_ (4_fluorobenzylidene) -1,1- Dimethyl ((methyl-phenyl-carbamyloxy) _) 1,2,3,6-tetrahydronitrocarbazone [4,5-b] indole-5-acrylic acid ethyl ester; 8- (2-dimethylaminoethylamine formamyloxy ) -3- (4-fluorobenzylidene) -1,1-dimethyl-1,2,3,6-tetrahydronitrogeno [4,5_b] ^ indole-5_carboxylic acid ethyl ester; 3 -(4-fluorobenzylidene) -1,1-dimethyl-8- (2-pyridine-2-yl · ethylamine formamyloxy) _1,2,3,6_tetrahydronitrogen Homo [4,5-b] indole · 5 · carboxylic acid ethyl ester; 3- (4-fluorobenzylidene) _1,1_dimethyldong (pyridinyl · methylamine formamyloxy) ) 1,2,3,6-tetrahydronitrogeno [4,5Hepta] indole-5-chinoic acid ethyl ester; 3- (4-fluorobenzyl) -1,1-dimethyl -8 · phenoxyhexyloxy-1,2,3,6-tetrahydro 85585 -48- 200307684 nitrogen benzo [4,5-b] indole-5-carboxylic acid ethyl ester; 8 · benzyloxycarbonyl Oxy-3--3- (4-fluorobenzylidene) -1,1-dimethyl-1,2,3,6_tetrahydronitrogeno [4,5hepta] oxindole-5-carboxylic acid ethyl Esters; and 8- (2-dimethylaminoethoxycarbonyloxy) -3- (4-fluorobenzylidene) -1,1-dimethyl-1,2,3,6-tetrahydronitrogen Ethyl [4,5-b] indole-5-carboxylic acid ethyl ester; 8- (tylmethylamino) -3- (3,4-difluorobenzylidene H, l-dimethyl- 1,2,3,6-tetrahydronitrogen is entrained [4,5 七] Etholin-5-carboxylic acid ethyl ester. 53. The compound according to item 2 of the scope of patent application; wherein: η is 0 or 1; A is -N (R9)-; R1 is -C (0) OR14; R2 is hydrogen; R3 is -C (0) R10 R4 is hydrogen, optionally substituted alkyl or -CXCOR1 8; R5, R6 and R7 are each independently hydrogen or optionally substituted alkyl; R8 is hydrogen, optionally substituted alkyl, self-grouped or -OR27; R9 is hydrogen; R1G is optionally substituted heterocyclyl or optionally substituted heteroaryl; R18 is optionally substituted alkyl; and R27 is optionally substituted alkyl. 54_ The compound according to item 53 of the scope of patent application, which is selected from the group consisting of the following: 3- (benzo [1,3] dioxolene-5-carbonyl) each methoxy-1,2,3, 6-tetrahydro-nitrogeno [4,5-b] indole-5-carboxylic acid ethyl ester; 3- (benzo [1,3] dioxolene-5_carbonyl) · ι, 2 ,, 3,6-tetrahydro-nitrogeno [4,5_b] 85585 -49- 200307684 ethyl indole-5-carboxylic acid; 3- (2,3-dihydro-benzo [ι, 4] dioxolane Limonene_6_carbonyl group, and ^ tetrahydrogen, [4,5_b] indole-5_carboxylic acid ethyl ester, 3_ (4_methyl_2_pyracin-2-yl-distazole-5 -Carbonyl) -1,2,3,6-tetrahydronitropyrene [4,5-Cetoindol-5 · carboxylic acid ethyl ester; 3- (2-phenphen-2-yl-distazole-4 · Carbonyl) -1,2,3,6-tetrahydro-nitrogeno [4,5hepta] oxindole-5-carboxylic acid ethyl ester; 3- (2-phenyl-thiazole-4-carbonyl) -1, 2,3,6-Tetrahydro-nitrogeno [4,5Hepta] oxindole-5-carboxylic acid ethyl ester; 3- (4-methyl-2-phenyl · xantulene · 5-carbonyl) -1 1,2,3,6-tetrahydro · nitrogeno [4,5_b] indole-5_resonate ethyl ester. 55. The compound according to item 2 of the scope of patent application; wherein: η is 0 or 1; Α is -N (R9) _; R1 is -C (0) 0R14; R2 is hydrogen; R3 is -C (0) N (Rn) R10; R4, R5, R6 R7 and R9 are each hydrogen; R8 is hydrogen, optionally substituted tiger, halo, or -OR2 7; R10 is optionally substituted aryl; R11 is hydrogen; R14 is optionally substituted alkyl; And R27 are optionally substituted alkynyl groups. 56. The compound according to item 55 of the scope of patent application is selected from the group consisting of the following: 85585 -50- 200307684 3-Ethyl-9- (2-methoxy -Phenyl) -i, 2,3,6-tetrahydro-nitrogeno [4,5hepta] indole-5-carboxylic acid ethyl ester; 3- (4-phenoxy-anilinemethyl-6- Tetrahydro-nitrogen [4,5-b] Windole-5-carboxylic acid ethyl ester; 3- (biphenyl-4-ylaminomethylamidino) · 1,2,3,6-tetrahydro-nitrogen Benzo [4,5-b] pyrene-5-carboxylic acid ethyl ester; 3- (3-phenoxy-anilinemethyl) -1,2,3,6-tetrahydro-nitrogeno [4, 5 hepta] oxindole-5-carboxylic acid ethyl ester; φ 3_ (hydroindene_5_ylaminomethylmethyl) -1,2,3,6-tetrahydro-nitrogeno [4,5 hepta] pyrene -5-Ethyl carboxylate 57. The compound according to item 2 of the scope of patent application; wherein: η is 0; A is -N (R9)-; R1 is -C (0) 0R14; R2 is hydrogen; R3 is -C (0) N (Ru) R10; # R4, R5, R6, R7, R8 and R9 are each hydrogen; R10 is optionally substituted alkyl, Optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, or optionally substituted heteroaryl; R11 is hydrogen or optionally substituted alkyl; and R14 is Optionally substituted alkyl. 58. The compound according to item 57 of the scope of patent application, which is selected from the group consisting of 3- (3 · methylthio-anilinomethyl) -1,2,3,6-tetrahydro-nitrogen [ 4,5Hepta] indole-5- 85585 -51- 200307684 ethyl carboxylate; 3- (4-fluoro-benzylaminemethylamidino) -1,2,3,6-tetrahydro-nitrogen [4,5 Hepta] oxindole-5-acetic acid ethyl ester; 3-benzylamine formamyl-1,2,3,6-tetrahydro-nitrogeno [4,54)] 4 indole-5 -Ethyl carboxylate. 59. The compound according to item 2 of the scope of patent application; wherein: η is 0 or 1; A is -N (R9) _; R1 is -C (0) 0R14; R2 is hydrogen; R3 is ((OPR10; R4 , R5, R6, R7, and R9 are each hydrogen; R8 is hydrogen, optionally substituted alkyl, halo, or -OR2 7; R10 is optionally substituted tiger, optionally substituted aryl, or optionally Optionally substituted aralkyl; R11 is hydrogen or optionally substituted alkyl; _ R14 is optionally substituted alkyl; and R27 is optionally substituted alkyl. 60 · According to Patent Application No. 59 The compound of the item, which is selected from the group consisting of the following: 8-methoxy-1,6-dihydro-2H-azepine [4,5 hepta] indole-3,5-dicarbamic acid 5-ethyl ester 3 -Phenyl ester; 8-fluoro-1,6-dihydro-2H-nitrogeno [4,5-b] indole-3,5-dicarboxylic acid 5-ethyl 3-phenyl ester. 61. According to Compound No. 2 in the scope of patent application; of which: 85585 • 52- 200307684 XI is 0 or 1; A is _N (R9) _; R1 is -C (0) OR14; R2 is hydrogen; R3 is -S (0 ) 2R10; R4, R5, R6, R7 and R9 are each hydrogen; R8 is hydrogen or -OR27;-R10 is optionally substituted aryl or optionally Instead, heteroaryl 'R11 is hydrogen or optionally substituted alkyl; R14 is optionally substituted alkyl; and R27 is optionally substituted alkyl. 62. Compound according to item 51 of the scope of patent application , Which is selected from the group consisting of the following 3- (toluene-4_mercapto) -1,2,3,6-tetrahydro-nitrogeno [4,5 七] ; 3- (4-Chloro-benzenesulfonyl) -1,2,3,6-tetrahydro-nitrogen benzo [4,5-b] Windole-5-carboxylic acid isopropyl ester; H4-methoxy -Benzenesulfenyl) · ι, 2,3,6_tetrahydro · nitrogeno [4,5hepta] indole-5-carboxylic acid isopropyl ester; 3_ (3,4_dimethoxy- Benzenesulfonyl) 1,2,3,6 · tetrahydro · nitrogeno [4,5-bH indole-5-isopropanoic acid isopropyl ester; 3 difluoromethoxy-benzenesulfonyl) -1 , 2,3,6-tetrahydro-nitrogen hydride [4,5 七] &lt; Indole-5-isopropanoic acid isopropyl g. 63. The compound according to item j of the stated patent, wherein the compound is a compound of formula ⑽: 85585 200307684 Or a pharmaceutically acceptable derivative thereof, wherein: η is 0 to 4; A is -N (R9)-, -0-, or -S (0) t- (wherein t is 0 to 2); R1 is regarded as Optionally substituted alkynyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally Case substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, -01114, _1 \ [(1115) 1116, call (1117)] ^ (1115) 1116,- (: (0) 1118, -C (0) 0R14, -C (S) OR14, -C (0) SR14, -C (0) N (R15) R16, -C (0) N = NR16 or 7) Ν (Ι ^ 5) Ri6; R2 is hydrogen or optionally substituted alkyl; or R1 and R2 and the atom to which they are connected together to form a substituted cycloalkyl, optionally substituted hetero Ring group, optionally substituted aryl or optionally substituted heteroaryl ring; R3 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally Optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aryl, Case substituted heteroaryl, optionally substituted heterocyclic, optionally substituted heteroaralkyl, ((0) 111 〇, _C (0) OR1 (), -8 (0) 2 ^ 1. _C (0) N (R &quot;) R10 ^ ^ (Ο) Ν (Κ11) Ν (^ 2 -KR11) 0 (0) ^ 0 ^ ^ (R11) 0 (〇) ^^ 2) R) 0 85585 -54- 200307684 '-N (Ru) C (0) N (R12) N (R13) R10' -NCR11) 0 (0) 0 ^ 0 '-P (〇) 〇R10 or -p (o) (or19) or10; R4 is hydrogen, optionally substituted alkyl, optionally substituted feminine, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, Optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, -C (0) R18, _c (o) or2. , -C (0) N (R21) R22 or _ C (0) N (R42) N (R21) R22; R5, R6, and R7 are each independently hydrogen, optionally substituted alkyl, or optionally substituted Aralkyl, optionally substituted heteroaralkyl, -〇1 ^ 14, -S (0) 2R14, -N (R15) R16, _C (0) R18, -C (0) 0R2 (), or- C (0) N (Rn) R22: or R4 and R7, or R4 and R5, or R4 and R6, or R5 and R7, or R5 and R6 'or R6 and R7, one Forms optionally substituted cycloalkyl, optionally substituted heterocyclyl, or optionally substituted cycloalkenyl rings; and other R4'R5, R6, and R7 are as described above; or R4 and R5 together form a keto group ; And R6 and R7 are as described above; or R6 and R7 together form a keto group; and "and! ^ All are as above; each R8 is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted 4aryl, and optionally substituted Heteroaryl, _yl, pseudopyridyl, cyano, nitro, -C (〇) 〇R2 3, c (〇) n (r24) r25, ((〇) r26, -〇r27, sr27 and _ N (R28) R29; R9 is hydrogen, optionally substituted alkyl or _s (〇) 2R43; 85585 -55- 200307684 Rio, R11, R12, R13 and R19 are in ⑻ or (b) as described below Choice: ⑻R11, R12, R13 and R19 are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted Substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; and r1 G is optionally substituted Substituted alkynyl, optionally substituted amidino, optionally substituted block 1 base, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aromatic Base, optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; or "^ and 1111, and / or R1G and R12, and / or R1G and R13 And / or R1G and R19, and / or R11 and R12, and / or R12 and R13, together with the atoms to which they are attached, form a heterocyclic ring optionally substituted or a heteroaryl ring optionally substituted; The other R10, R11, R12, R13, and R19 are selected as above; R14, R15, R16, and R17 are selected as such or (b) ... R14, R15, R16, and R17 are each independently hydrogen , Optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aralkyl , Optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; or ⑼R15 and R16 and the nitrogen atom to which they are connected together to form a optionally substituted hetero Cyclic ring or optionally substituted heteroaryl ring, while R14 and R17 are selected as above, R18 is selected as appropriate Resistant base, optionally substituted fluorenyl, substituted 85585 -56- 200307684 optionally substituted alkynyl, optionally substituted cycloalkynyl, optionally substituted aryl, optionally substituted aralkyl 2, optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; R20, R2 1, R22 &amp; R42 are selected from the following ⑻ or ⑼: ⑻! ^, R2 1, R22 and R42 are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted Substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; or (b) R21 and R22 and The nitrogen atoms to which they are connected together form an optionally substituted heterocyclyl ring or an optionally substituted heteroaryl ring, and R2G and R42 are selected as above; R23, R24, R25 and R26 Choose from ⑻ or (b) as follows: ⑻R23, R24, R25, and R26 are each independently hydrogen. Substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally Substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; or (b) R24 and R25 and the nitrogen atom to which they are attached together to form a optionally substituted heterocyclic ring Or optionally substituted heteroaryl ring, and R23 and R26 are selected from ⑻ as above; R27, R28 and R29 are selected from ⑻ or (b) as follows: ⑻R27, R28 and R29 are each independent Hydrogen, optionally substituted alkyl, optionally substituted fluorenyl, optionally substituted alkynyl, optionally substituted aryl, 200307684 optionally substituted aromatic alkyl, optionally substituted Heteroaryl, optionally substituted heteroaralkyl, _C (〇) R3 G, -C (0) 0R31 or -C (〇) N (R3 2) R3 3: or (b) R2 8 and R2 9 and the nitrogen atom to which they are attached together form a heterocyclic ring optionally substituted or a heteroaryl ring optionally substituted, and r27 is as above R3 0 is hydrogen, optionally substituted alkyl, optionally substituted amidino, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, Optionally substituted aromatic radical, optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; R3 1 is optionally substituted alkyl, optionally Substituted fluorenyl, optionally substituted alkynyl, optionally substituted cycloalkynyl, optionally substituted aryl, optionally substituted aromatic alkyl, optionally substituted heterocyclyl, Optionally substituted heteroaryl or optionally substituted heteroaralkyl; R3 2 and R3 3 are selected from the following ⑻ or 下述: ⑻r3 2 and R3 3 are each independently hydrogen and optionally substituted Alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aromatic alkyl, optionally Substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted heteroaryl ; Or (b) R3 2 and R3 3 and the nitrogen atom to which they are attached together to form a heterocyclic ring optionally substituted or a heteroaryl ring optionally substituted; R43 is a substituted alkyl substituted as appropriate Base, optionally substituted alkenyl, optionally substituted decyl, optionally substituted cycloalkenyl, optionally -58- 85585 200307684 substituted aromatic, optionally substituted aromatic Optionally substituted heterocyclic group, optionally substituted heteroaryl group, or optionally substituted heteroaryl group; each R1 _R3 3, R4 2 and R4 3, when substituted, are substituted by one or more Each independently selected from the substituents of Q1; Q1 is a _ group, a pseudohalo group, a hydroxyl group, a keto group, a thio group, a nitrile, a nitro group, a formate group, a mercapto group, a carbonyl group, a fluorenyl alkyl group, an alkyl group, Alkyl, polyhaloalkyl, aminoalkyl, diaminoalkyl, alkenyl containing 1 to 2 double bonds, alkynyl containing 1 to 2 reference bonds, cycloalkyl, cycloalkylalkyl , Heterocyclyl, heterocyclylalkyl, aryl, heteroaryl, aralkyl, arkenyl, aralkynyl, heteroaralkyl, trialkylsilyl, dialkylarylsilyl , Alkyldiarylsilyl, triarylsilyl, alkylene, arylalkylene, alkylcarbonyl, cycloalkylcarbonyl, heterocyclylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, Alkoxycarbonylalkyl, aryloxycarbonyl, aryloxycarbonylalkyl, aralkyloxycarbonyl, aralkyloxycarbonylalkyl, arylcarbonylalkyl, aminocarbonyl, alkylamino, dioxane Amino carboxyl, arylamino carbonyl, diarylamino alkynyl, arylalkylaminocarbonyl, alkoxyaryloxy, heteroaryloxy, heteroaryloxy, heterocyclyloxy, ring Alkoxy, perfluoroalkoxy, fluorenyloxy, alkynyloxy, aralkyloxy, alkoxycarbonyl, arylcarbonyloxy, aralkylcarbonyloxy, alkoxycarbonyloxy, aryloxy Carbonyloxy, aralkyloxycarbonyloxy, aminocarbonyloxy, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylarylaminocarbonyloxy, diarylaminocarbonyloxy Group, guanidine, isothiourea group, formamyl group, tigeryl formamyl group, aryl formamyl group, aminothiocarbonyl group, 85585 -59- 200307684 alkylaminothiocarbonyl group, arylamino group Thiocarbonyl, amine, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, arylaminoalkyl, diarylaminoalkyl, alkylarylaminoalkyl, alkylamino , Dialkylamino, haloalkylamino, arylamino, diarylamino, alkylarylamino, alkylcarbonylamino, alkoxycarbonylamino, aralkyloxycarbonylamino, aryl Carbonylamino, arylcarbonylaminoalkyl, aryloxycarbonylaminoalkyl, aryloxyarylcarbonylamino, aryloxycarbonylamino, alkylsulfonylamino, arylsulfonyl Amine, heteroarylsulfonylamino, heterocyclylsulfonamido, heteroarylthio, azide, diazenyl, -n + (r34) (r35) r36, -p (R37 ) 2, -p (o) (r37) 2, -〇P (〇) (R3 7) 2, -n (r38) c (o) r39, dialkylphosphonic acid group, alkylarylphosphonic acid group, Diarylphosphonic acid, hydroxyphosphonic acid, alkylthio, arylthio, perfluoroalkylthio, hydroxycarbonylalkylthio, thiocyano, isothiocyano, alkylsulfinyloxy Alkyl, alkylsulfonyloxy, arylsulfinyloxy, arylsulfonyloxy, hydroxysulfonyloxy, alkoxycarboxylic acid Amine amino acid sulfonyl amine, sulfonyl amine sulfonyl oxy, diamine sulfonyl sulfonyl oxy, aryl amine sulfonyl oxy, diaryl amine sulfonyl oxy, alkylaryl amine sulfonyl Alkoxy, sulfosulfanyl, alkylsulfinyl, alkylsulfonyl, arylsulfinyl, arylsulfinyl, hydroxysulfinyl, sulfonylsulfonyl, amino Fluorenyl, sulfonylamino, sulfonyl, sulfonylaminosulfonyl, arylaminosulfonyldiarylaminosulfonyl, or alkylarylaminosulfonyl; or two Q1 groups, Its substituted atoms are in a 1,2 or 1,3 arrangement 'together to form an alkylene, oxyalkylene, alkylenedioxy, thioalkyloxy or alkylenedithio group; or 85585- 60- 200307684 Two Q1 groups, which are substituted with the same atom, together form an alkylene group; R34, R35, and R36 are each independently hydrogen, alkyl, aryl, aralkyl, heterosquatyl, tetragonal, Heterocyclyl or heterocyclyl; R37 is hydroxyl, alkoxy, aralkoxy, alkyl, heteroaryl, heterocyclyl, aryl, or -nr4Gr41; R4G and R41 are each independently hydrogen or alkyl , Aralkyl, aryl, heteroaryl, A square alkyl group or a heterophenyl group, or R4 G and R41 together form a secondary alkyl group, a nitrophenylene group, an oxyalkylene group, or a thioalkylene group; R38 is hydrogen, an alkyl group, an aryl group, an aralkyl group, Heteroaryl, heteroaralkyl, heterocyclyl or heterocyclyl; and R39 is alkoxy, aralkyloxy, alkyl, heteroaryl, heterocyclyl, aryl, or -N (R4 ( )) R41; each Q1 is independently unsubstituted, or is substituted by one or more substituents each independently selected from Q2; each Q2 is independently halo, pseudohalo, aryl, keto, thio, Nitrite, nitro, formamyl, fluorenyl'hydroxycarbonyl, hydroxycarbonylalkyl, alkyl, alkyl, polydentate, aminoalkyl, diaminoalkyl, containing 1 to 2 Alkyl group of double bond, alkynyl group containing 1 to 2 references, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, heteroaryl, aralkyl, aryl Base, aralkynyl, heteroaralkyl, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, alkylene, arylalkylene, alkylcarbonyl , Cycloalkylcarbonyl, heterocyclylcarbonyl, arylcarbonyl Heteroarylcarbonyl, alkoxycarbonyl, alkoxycarbonylalkane 85585 -61- 200307684, aryloxycarbonyl, aryloxycarbonylalkyl, aralkyloxy, aralkyloxycarbonylalkyl, arylcarbonyl Alkyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl, diarylaminocarbonyl, aralkylaminocarbonyl, alkoxyaryloxy, heteroaryloxy, Heteroaralkoxy, heterocyclyloxy, cycloalkoxy, perfluoroalkoxy, diluteoxy, blockoxy, aralkoxy, alkcarbonyloxy, arylcarbonyloxy, aralkyl Carbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, aralkyloxycarbonyloxy, aminocarbonyloxy, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylaryl Aminocarbonyloxy, diarylaminocarbonyloxy, guanidine, isothiomethyl, formamyl, alkylmethyl adenyl, arylformyl, sulfonyl Base, arylaminothio, amine, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, arylaminoalkyl, diarylaminoalkyl, alkylarylamino alkyl , Alkylamino, dialkylamino, commercial alkylamino, arylamino, diarylamino, alkylarylamino, alkylcarbonylamino, alkoxycarbonylamino, aralkyloxycarbonylamine Aryl, arylcarbonylamino, arylcarbonylaminoalkyl, aryloxycarbonylaminoalkyl, aryloxyarylcarbonylamino, aryloxycarbonylamino, alkylsulfonylamino, aryl Hexanoic acid amino group, heteroarylcontinylamino group, heterocyclylamino group, heteroarylthio group, azido group, diazenyl group, -N + (r34) (r35) r36, -P (R37) 2, 100X113%, -0 (0) (R37) 2, to take 38) (: (〇) 1139, dialkyl phosphonate, alkyl arylphosphonate, diaryl Phosphonate, dinylphosphonic acid, alkylthio, arylthio, perfluoroalkylthio, mesitylthio, thiocyano, isothiocyano, alkylsulfinyloxy , Alkylsulfonyloxy, arylphosphinoyloxy, arylsulfanyloxy, mesityl 85585 -62- 200307684oxy, alkoxysulfonyloxy, aminosulfonyloxy Alkyl, alkylaminosulfonyloxy, dialkylaminosulfonyloxy, arylaminosulfonyloxy, diarylamine Benzyloxy, aryl arylamino, fluorenyloxy, thiol, sulfinyl, sulfonyl, alkylsulfonyl, arylsulfinyl, arylsulfonyl, hydroxy Fluorenyl, alkoxyl, amine, amine, amine, diamine, cyano, arylamino, phenylamino, diarylamino, fluorenyl, or arylarylamine Amino acid group; or two Q2 groups, the substituted atom system of which is 1, 2 or 1, 3, together form an alkylene group, oxyalkylene group, alkylenedioxy group, thioalkyloxy group Or an alkylidenedithiooxy group; or two Q groups, which are substituted with the same atom and together form a hypocarbyl group, with the proviso that if R8 is hydrogen or _〇CH3, trans 3 is not hydrogen or methyl. Group, ethenyl group, _ch2c6h5, _CH (CH3) C6H5, CH (CH3) fluorenyl group, or c (o) oc2h5, and the condition is that if R3 is hydrogen, R8 is not hydrogen, nitro, or Alkoxy, aryl or hydroxy. 64. The compound according to item 63 of the scope of patent application, wherein: η is 0; A is -N (R9)-; R1 is -qopR14 or 5) R1 6; R2 is hydrogen; R is gas, optionally substituted Aryl, _C (〇) ri 〇; 〇; or -C (0) N (Ru) Ri〇; R4, R5, R6, R7, and R9 are each hydrogen; 85585 -63 · 200307684 R is optionally substituted Aryl or optionally substituted aralkyl; Rl 1 is hydrogen; Rl 4 is optionally substituted alkyl; Rl 5 is hydrogen; and R16 is optionally substituted alkyl or optionally substituted Of aralkyl. 65_ — A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound according to item 1 of the patent application. 66. The pharmaceutical composition according to item 65 of the scope of patent application, wherein the pharmaceutical composition further comprises at least one other active agent selected from the group consisting of an antihyperlipidemic agent, a plasma HDL-raising agent, an antihypercholesterol agent, and a cholesterol biosynthesis inhibitor Agent, HMG CoA reductase inhibitor, fluorenyl-coenzyme a cholesterol glutamyl transferase (ACAT) inhibitor, probucol (prObuc〇1), raloxifene, Test amines, cholesterol absorption inhibitors, bile acid sequestrants, low-density lipoprotein receptor derivatives, clofibrate, fenofibrate, benzofibrate ), Cipofibrate, gemfibrizol, vitamin B6, vitamins &amp; 2, vitamin C, vitamin e, less blockers, antidiabetic agents, sulfonylureas, biguanide , Oxazolidinediones, activators of PPARa, PPAR cold and PPARr, dehydroepiandrosterone, anticorticoids, tnf alpha inhibitors, ck-glucosidase inhibitors, pramlintide, Dextrin, insulin, angiotensin II antagonist Angiotensin-converting enzyme inhibitor, platelet aggregation inhibitor, fibrinogen receptor antagonist, LXR alpha activator 'antagonist or partial activator, LXR / 3 activator, antagonist or partial activator Molecules, phenylpropanolamine, phentermine 85585 200307684, diethylamine phenone, chlorphenimide K 丨 thumb, fenfluramine, dexfenfluramine, fentilira Phentiramine, / 53 adrenergic receptor activator, sibutramine, gastrointestinal lipase inhibitor, neuropeptide Y, entry nystatin, cholangiogenin, pombesin ), Dextrin, histamine Η; receptor activators or antagonists, dopamine D2 receptor 4 隹 agonists or antagonists, melanocyte stimulating hormone, adrenocorticotropic hormone releasing factor, leptateine, galangal Or T-aminobutyric acid (GABA), aspirin or fibric acid derivatives. &amp; A method for treating, preventing or ameliorating one or more symptoms of a disease or condition in which nuclear receptor activity is implicated, which comprises administering to a patient in need thereof an effective amount of a compound according to item 1 of the scope of patent application. 68. The method according to item 67 of the patent application, wherein the disease or disorder is selected from the group consisting of hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, dyslipidemia, dyslipidemia, atherosclerosis, atherosclerosis Tumor sclerosis, atherosclerotic disease event, atherosclerotic heart and vascular disease, syndrome X, diabetes, type 2 diabetes, insulin insensitivity, hyperglycemia, bile stagnation and obesity. 69. The method of claim 67, wherein the disease or condition is selected from the group consisting of hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, and dyslipidemia. 70. The method according to item 67 of the application, wherein the disease or condition is selected from the group consisting of atherosclerosis, atherosclerotic disease, atherosclerotic disease event, and atherosclerotic 71. According to the application The method of the patent Fan Yuan item, wherein the disease or condition is selected from 85585 200307684, and the insulin-insensitive disease or condition is a blood self-included symptom X, diabetes, type π diabetic and southern blood glucose. 72. The method according to item 67 of the patent application park, wherein the fat is excessive. 73. The method according to claim 67, wherein the disease or condition is hypertriglyceridemia. The method according to item 67 of the patent application, wherein the disease or condition is hypercholesterolemia. A method according to item 67 of the patent application, wherein the disease or condition is obesity. 76. The method according to item 67 of the application, wherein the disease or condition is bile stagnation. 77. The method according to item 67 of the application, wherein the compound is a farnesin X receptor activator, a partial activator, a partial antagonist or an antagonist.笊 The method according to item 67 of the application, wherein the nuclear receptor is a farnesin X receptor. 79. The method according to item 68 of the scope of patent application, wherein the method further comprises administering at least one other active agent selected from the group consisting of an antihyperlipidemic agent, a plasma booster, and an antihypertensive agent at the same time, before, or after the administration of the compound. Cholesterolemia agents, cholesterol biosynthesis inhibitors, reductase inhibitors, phospho-coenzyme A cholesterol phosphotransferase (ACAT) inhibitors, probucol, raloxifene, tested Acid, alkalamine, cholesterol absorption inhibitor, bile acid sequestering agent, low-density lipoprotein receptor peptide, clofibrate, fenofibric acid target 85585 -66- 200307684 ( fenofibrate), benzofibrate, cipofibrate, gemfibrizol, vitamin B6, vitamins &amp; 2, vitamin C, vitamin E, / 3-blocker, anti Diabetes, sulfonylureas, bisguanidine, piexitide dione; activators of PPARa, PPAR stone and PPARy, dehydroepiandrosterone, anticorticoid, TNFa inhibitor, α-glucose Enzyme inhibitor, pramli ntide), dextrin, insulin, angiotensin II antagonist, angiotensin converting enzyme inhibitor, platelet aggregation inhibitor, fibrinogen receptor antagonist, LXR alpha activator, partial activator or antagonist Agents, LXR without stimulants, partial stimulants or antagonists, phenylpropanolamine, phentermine, diethylamine phenone, clomiphene, fenfluramine, Dexfenfluramine, phentiramine, / 33 epinephrine receptor activator, sibutramine, gastrointestinal lipid inhibitors, neuropeptide Y, enter bacteriostasis Hormone, cholangiogenin, bombesin, dextrin,% histamine receptor agonist or antagonist, dopamine D2 receptor agonist or antagonist, melanocyte stimulating hormone, adrenocorticotropic hormone release Factor, lepasu, galangin or raminobutyric acid (GABA), aspirin or fibric acid derivative. 80. A method according to item 68 or 69 of the scope of patent application, wherein the method further comprises administering at least one other active agent at the same time as &lt; before or after administration of the compound according to item 1 of the scope of patent application, Selected from antihypertensive agents, plasma HDL-raising agents, antihypercholesterolemia agents, cholesterol biosynthesis inhibitors, HMGCoA reductase inhibitors, fluorenyl-coenzyme octacholesterol phosphotransferase (ACAT) inhibitors, Probub can be turned around, induced by ralox 85585 -67- 200307684, raloxifene, acid test, amine test, cholesterol absorption inhibitor, bile acid sequestrant, low density lipoprotein receptor Compounds, cloofibrate, fenofibrate, benzofibrate, cipofibrate, gemfibrizol, vitamins, vitamins &amp; 2.Antioxidant vitamins, / 3-blockers, antidiabetic agents, angiotensin II antagonists, angiotensin converting enzyme inhibitors, platelet aggregation inhibitors, fibrinogen receptor antagonists, aspirin , LXR alpha activator, partial activator or antagonist, LXR / 3 activator, partial activator or antagonist, or fibric acid derivative. 81. A method according to item 71 of the scope of patent application, wherein the method further comprises administering at least one other active agent selected from the group consisting of sulfonylureas, bisguanidine, pyrimidine, at the same time, before, or after the administration of the compound Zolidinediones; PPARa, PPAR / 3, and PPARr activators; activators, LXR α activators, partial activators or antagonists, LXR / 3 activators, partial activators or antagonists Agents, dehydroepiandrosterone; anticorticoids; TNFa inhibitors; alpha-glucose inhibitors, pramlinide, dextrin, or tenosin. 82. A method according to item 72, 73, 74, or 75 of the scope of patent application, wherein the method further comprises administering at least one other active agent selected from the group consisting of phenylpropanolamine, at the same time, before, or after the administration of the compound. Phentermine, diethylamine phen i, chlorobenzimidazole, fenfluramine, dexfenfluramine, phentiramine, cold 3 epinephrine Receptor activator, sibutramine, gastrointestinal lipase inhibitor, LXR α activator, partial activator or antagonist, LXR / 3 activator 85585 -68- 200307684 activator, partial activator Activator or antagonist, neuropeptide γ, enterostatin, cholangiogenin, bombesin, dextrin,% histamine receptor agonist or antagonist, dopamine D2 receptor activator or Antagonists, melanocyte-stimulating hormone, corticotropin-releasing factor, laparone, galangin, or 7-aminobutyric acid (GABA). 83. The method according to item 68 of the scope of patent application, wherein the compound is a compound of formula (i)): 84. — A kind of prevention or reduction in patients from hyperlipidemia, hypercholesterolemia, hyperglycerideemia, dyslipidemia, dyslipidemia, atherosclerosis, atherosclerotic disease, Atherosclerotic disease event, atherosclerotic heart and vascular disease, syndrome x diabetes, type 2 diabetes, insulin insensitivity, high blood sugar, risk of bile stagnation and obesity, or methods of its complications, This includes administering a prophylactically effective amount of a compound according to item 1 of the scope of the patent application. 85_ — A method for reducing plasma cholesterol levels in a patient in need, which comprises administering an effective amount of a compound according to the scope of the patent application. 86. A method for reducing plasma triglyceride content in a patient in need, which comprises administering an effective amount of a compound according to the scope of the patent application. 87. A treatment, prevention or amelioration of diseases that are affected by abnormal cholesterol, triglycerides or bile 85585 -69- 200307684 Juicy acid content or which includes administering the compound of item 1 to a patient in need. A method for exposing one or more symptoms, an effective amount according to the scope of patent application 88.-a method for modulating cholesterol metabolism, catabolism, human formation, absorption, reabsorption, secretion or excretion in money-feeding materials The amount is based on the compound in the scope of application for item i. 89. A method for modulating triglyceride metabolism, catabolism, synthesis, absorption, reabsorption, secretion or excretion in mammals, which comprises administering an effective amount of a compound according to item 1 of the scope of the patent application. 90 · —A method for modulating bile acid metabolism, catabolism, synthesis, absorption, reabsorption, secretion, excretion or bile acid pooling composition in mammals, which comprises administering an effective amount of Compound. 200307684 (1) Designated representative map: (1) The designated representative map in this case is: (). (2) Brief description of the representative symbols of the components in this representative map: 捌 、 If there is a chemical formula in this case, please disclose the chemical formula that best shows the characteristics of the invention: 85585